Initial Genome Sequencing and Analysis of Multiple Myeloma - Supp

SUPPLEMENTARY INFORMATION
doi:10.1038/nature09837
Patients with MM (n=38)

Tumor (aspirate)
Normal (blood)
CD138 selection
Ficoll purification
WGS libraries (n=23)
Exome hybrid capture (n=16)
Mean 32.8X
coverage
Mean 104.4X
coverage
WGS libraries (n=23)
Exome hybrid capture (n=16)
Mean 32.2X
coverage
Mean 110.3X
coverage
Illumina
sequencing
Calibrate quality scores
Align to genome
Mark duplicate reads
BAM file
Quality control
Mutector algorithm
(point mutations)
Indelocator algorithm
(< 22 bp indels)
dRanger algorithm
(> 600 bp indels, inversions, translocations)
Supplementary Figure 1 Sequencing and analytical pipeline for determining somatic mutations in MM.
WWW.NATURE.COM/NATURE | 1
RESEARCH SUPPLEMENTARY INFORMATION
doi:10.1038/nature09837
WE
Sensitivity:
WGS
24
14
24
67% (all exons)
(All exons)
(WE targeted
exons)
88%
88% (targeted exons)
Supplementary Figure 2 Sensitivity estimations. Sample MMRC0191 was sequenced by both WGS and
WES. To estimate sensitivity, supporting reads for each nonsynonymous mutation were assessed manually and
likely false positives discarded. Then mutations were placed in three groups: detected in WES only, detected in
both datasets, or detected in WGS only. These numbers were used to assess sensitivity of the two sequencing
methods (upper set of numbers in Venn diagram). A number of mutations that were detected by WGS only were
not targeted by the hybrid capture bait set, so to assess the sensitivity of the muTector caller in WES (as opposed
to the library production method), these were excluded from the analysis (lower set of numbers in Venn diagram).
doi:10.1038/nature09837
(a)
(b)
Supplementary Figure 3 Base- and region-specific somatic mutations rates. (a) Mutation rates by basespecific change. Error bars are estimated s.d. (b) Mutation rates by base-specific change in different genomic
regions. Error bars are estimated s.d.
doi:10.1038/nature09837
1000
1,000
Normalized expression
n
n
2,000
2000
1,800
1800
1,600
1600
1,400
1400
1,200
1200
1,000
1000
800
800
600
600
400
400
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200
00
-200
-200
600
600
400
400
200
200
00
MMRC dataset samples (n = 304)
200
200
180
180
160
160
140
140
120
120
100
100
80
80
60
60
40
40
20
20
00
-20
-20
800
800
Cell line samples (n = 52)
Arkansas dataset samples (n = 414)

Highest expressing of recurrent IgH translocation partners (one of CCND1, CCND3, FGFR3, MAF, MAFB, or WHSC1)
HOXA9
1,000,000
c
Genomic DNA
Relative HOXA9 expression
cDNA
100,000
10,000
MM outlier
1,000
100
MM non-outlier
10
1
MLL re-arranged
AML
Supplementary Figure 4 Patterns of HOXA9 expression in MM

MM. (a) Patterns of HOXA9 expression (red)
compared to those of canonical targets of IgH translocation (blue). (b) Ubiquitous expression of HOXA9 was
demonstrated by qPCR. Expression is relative to that of the lowest expressing cell line, JIM3, and values are
normalized to expression of -actin. Error bars are S.E.M. and represent a minimum of 4 technical replicates.
(c) Examples of sequencing traces across informative SNPs in MM samples with outlying HOXA9 expression
(top) and non-outlying HOXA9 expression (middle). Also included is an MLL-rearranged acute leukemia cell line
(bottom). The allele-specific patterns of expression were seen in 2/2 informative outliers, 9/9 informative nonoutliers, and 1/1 informative MLL-rearranged AML cell line.
doi:10.1038/nature09837
XG6 RNA
HOXA9
actin
XG6 protein
XG6 viability
Supplementary Figure 5 Knockdown of HOXA9 is associated with reduced viability in the MM cell line
XG6. HOXA9 mRNA expression (top) and protein expression (middle) was assayed three and five days
(respectively) post-infection with seven independent lentiviral constructs expressing shRNAs targeting HOXA9
and a control shRNA targeting luciferase (shLuc). XG6 viability ten days post-infection, as assessed by
CellTiterGlo, is shown in the lower panel. Error bars in both graphs are S.E.M. and represent a minimum of four
technical replicates (mRNA) or three experimental replicates (relative luminescence).
doi:10.1038/nature09837
Supplementary Figure 6 HOXA9 is essential for MM survival. GFP competition assay in MM cell lines.
Following lentiviral infection with seven independent shRNAs that target HOXA9 (blue) or a control shRNA
targeting luciferase (shLuc; red), GFP+ cells were monitored by flow cytometry and compared to the proportion of
GFP+ cells present in the population 3 days post-infection (designated day 0). Error bars are S.E.M. and
represent a minimum of three experimental replicates. Differences between GFP+ proportions at day 14 for shLuc
and targeting hairpins were significant for all hairpins in all cell lines apart from in KMS12-BM.
doi:10.1038/nature09837
Chromosome 7
Primary patien
nt samples (n = 254
4)
HOXA locus
Log2 ratio
copy number
+3
-3
Supplementary Figure 7 Focal amplifications at the HOXA locus. A copy number heatmap of the HOXA
locus and flanking regions in a set of 254 publicly available MM aCGH samples.
doi:10.1038/nature09837
U266
SKMM
M1
OPM
M2
OCI-My
y7
OCI-My
y5
1S
MM.1
L363
KMS12-P
PE
KMS12-B
BM
KMS
S11
JIM
M3
INA
A6
+v
ve
-v
ve
F3
TFPI
FGA
FGG
LDHA
Supplementary Figure 8 Expression of coagulation factors in MM cell lines. F3, TFPI, FGA, and FGG,
which were all found to be mutated, were assayed. F5, which is known to be expressed in cells of lymphocytic
origin, was not assessed. Positive controls are dermal fibroblasts (F3) or whole liver extract (remainder). An
LDHA control was used to ensure approximately even loading.
doi:10.1038/nature09837
Overview
Example: definition of regions in

stretch of chromosome 1
New x = center of window
New y = mean RP score in window
Obtain genome-wide regulatory

potential (RP) scores from regulatory
potential track in UCSC browser:
Move at 10 bp increments
100 bp
0.35
0.30
0.25
RP score
http://hgdownload.cse.ucsc.edu/
goldenPath/hg18/regPotential7X/
mask regions of somatic
hypermutation.
0.20
0.15
0.10
0.05
0
9000
Smooth RP scores by averaging in a

100 bp window moved at 10 bp
increments across genome.
9500
10000
Chromosome 1 position
10500
10500
0.35
0.30
Region
RP score
0.25
Region
Region
Region
Region
0.20
0.15
0.10
Generate discrete regions of

regulatory potential regions of
contiguous non-zero RP score.
0.05
0
9000
9500
10000
Chromosome 1 position
10500
2.38 x 106 RP regions genome-wide
For a given region:

Determine total good quality coverage
and total number of mutations across all
38 samples in each region.
Total good quality coverage of region

across allll samples,
l
N
Total mutations in region in all samples, n
Mean mutation rate across all regulatory
regions,
Use binomial test to calculate

probability of seeing at least observed
number of mutations in total area
covered. Correct for multiple
hypotheses testing.
N
p = 1 i (1 ) N i
i =0 i
Benjamini-Hochberg procedure,
2.38x106 observations.
Filtering
Exclude regions with: q > 0.25; mutations confined to a single sample; exclusively coding
mutations; identical mutations at an identical base (likely artifact); evidence of misalignment
artifact on manual review of reads (majority of included regions subjected to additional PCR
and Sanger sequencing).
Supplementary Figure 9 Identification of significantly mutated potential regulatory regions.
10500
doi:10.1038/nature09837
Supplementary Figure 10 Copy-number profiles showing tumor-in-normal contamination in two

samples sequenced by WGS. These samples were excluded from analysis. Tumor (T) lanes are shown on the
left and normal (N) lanes on the right. ST labels an independent aCGH profile for tumor MM-0417.
doi:10.1038/nature09837
WES
WGS
1.0
0.8
0.6
0.4
0.2
0
0.2
0.5
0.8
GC content
Not in bait set

Not covered by either method (e.g. unable to align)
Supplementary Figure 11 Genomic coverage by sample. In the main plot, samples are arranged in columns
and coverage is shown by a heat map (key on the right). Regions not targeted by the hybrid capture bait set are
arranged at the bottom of the coverage plot, as indicated. Otherwise, regions are ordered by coverage. GC
content is shown in the plot on the left.
doi:10.1038/nature09837
(a)
(b)
(c)
Supplementary Figure 12 Effect of coverage on power. (a) Power to detect genes mutated at frequencies of
20%, 15%, 10%, 5%, and 3% as significant, assuming uniform coverage. (b) As in (a), but recalculated to reflect
actual coverage achieved. (c) Distribution of loss of power due to actual coverage. For each gene, the power at
observed coverage was divided by the power assuming uniform coverage for each mutational frequency. The
mean of these ratios was then taken for each gene and the genes binned as shown.
doi:10.1038/nature09837
Supplementary Figure 13 Nonsynonymous somatic coding mutation rates in previously treated and
newly diagnosed patient samples are not significantly different. Error bars are estimated s.d. N.S., not
significant.
doi:10.1038/nature09837
Supplementary Figure 14 Defined regions of regulatory potential (RP regions) have a lower mutation
rate than the remainder of the genome. Region-specific and overall mutation rates are shown for the RP and
non-RP regions. Error bars are estimated s.d.
doi:10.1038/nature09837
SupplementaryMethods
Contents
Sequencedatageneration............................................................................................................................2
WholeGenomeShotgun(WGS)LibraryConstruction..............................................................................2
WholeExome(WE)CaptureLibraryConstruction...................................................................................3
Illuminasequencing..................................................................................................................................3
Sequencedataprocessing............................................................................................................................3
Thesequencingdataprocessingpipeline.................................................................................................4
(1)Basequalityrecalibration................................................................................................................4
(2)Alignmenttothegenome................................................................................................................4
(3)Aggregationoflaneandlibraryleveldata.....................................................................................4
(4)Markingofduplicatedreads............................................................................................................4
TheCancerGenomeAnalysispipeline(Firehose).................................................................................5
(1)Qualitycontrol.................................................................................................................................6
(2)LocalRealignment...........................................................................................................................7
(3)Somaticsinglenucleotidevariationdetection................................................................................7
(4)Detectionofshortinsertionsanddeletions....................................................................................9
(5)Identificationofchromosomalrearrangements...........................................................................10
(6)Calculationofcoverage.................................................................................................................11
(7)Backgroundmutationratecalculation..........................................................................................12
(8)Identificationofsignificantlymutatedgenes................................................................................12
(9)Identificationofsignificantlymutatedregionswithregulatorypotential....................................13
(10)Assessmentofthefunctionalimpactofmutations.....................................................................14
Othermethods............................................................................................................................................15
doi:10.1038/nature09837
Publiclyavailableexpressionandcopynumberdatasets.......................................................................15
Genesetenrichmentanalysis(GSEA)forFAM46Ccoexpressedgenes................................................15
Outliersumstatistic(OSS)calculation....................................................................................................15
Celllines..................................................................................................................................................16
RTPCR.....................................................................................................................................................17
AssessmentofHOXA9proteinexpression..............................................................................................17
AssessmentofHOXA9mRNAexpression...............................................................................................17
Chromatinimmunoprecipitation(ChIP)assayforhistone3lysine27trimethyl(H3K27Me3)promoter
enrichment..............................................................................................................................................17
HOXA9knockdown................................................................................................................................18
shRNAconstructs................................................................................................................................18
Generationofvirusforknockdown...................................................................................................18
AssessingdegreeofHOXA9knockdown...........................................................................................18
AssessingeffectsofHOXA9knockdown.............................................................................................18
DeterminationofDIS3andFAM46Cmutationstatusincelllines.........................................................19
References..................................................................................................................................................19
Sequencedatageneration
WholeGenomeShotgun(WGS)LibraryConstruction
Wesheared13gofgenomicDNAtoarangeof100700bpusingtheCovarisE210instrument.DNA
fragmentswereendrepairedandphosphorylated,followedbyadenylationof3ends.Standardpaired
endadaptorswereligatedaccordingtothemanufacturersprotocol(Illumina).WeperformedQiagen
minelutecolumnbasedcleanupsbetweenallenzymaticsteps.Adapterligatedfragmentswerepurified
withpreparatorygelelectrophoresis(4%agarose,85volts,3hours)andtwobandswereexcised(500
520bpand520540bp)resultingintwolibrariespersamplewithinsertsaveraging380bpand400bp
respectively.DNAwasextractedfromgelbandsusingQiagenminelutecolumns.Theentirevolumeof
finalpurifiedfragmentswasenrichedviaPCRwithPhusionpolymerasefor10cycles.
EachoftheresultingWGSlibrarieswassequencedonanaverageof39lanesofanIlluminaGAII
sequencer,using101bppairedendreads,withtheaimofreaching30Xaveragegenomiccoverageof
doi:10.1038/nature09837
distinctmoleculespersample.Themeancoverageachievedwas33Xinthetumorsand32Xinthe
normals.
WholeExome(WE)CaptureLibraryConstruction
WefollowtheproceduredescribedbyGnirkeetal.1adaptedforproductionscaleexomecapturelibrary
construction.ExometargetsweregeneratedbasedonCCDSgenes,representing164,687exonsfrom
~16,500genes(representing93%ofknown,nonrepetitiveproteincodinggenesandspanning~1%of
thegenome).DNAoligonucleotideswerePCRamplified,thentranscribedinvitrointhepresenceof
biotinylatedUTPtogeneratesinglestrandedRNAbait.GenomicDNAfromprimarytumorand
patientmatchedbloodnormalwassheared,ligatedtoIlluminasequencingadapters,andselectedfor
lengthsbetween200350bp.ThispondofDNAwashybridizedwithanexcessofbaitinsolution.The
catchwaspulleddownbymagneticbeadscoatedwithstreptavidin,theneluted.
Resultingexomesequencinglibrariesfromtheprocessdescribedaboveweresequencedonthreelanes
ofanIlluminaGAIIsequencer,using76bppairedendreads1.Themeancoverageachievedwas104Xin
thetumorsand110Xinthenormals.
Illuminasequencing
LibrarieswerequantifiedusingaSYBRGreenqPCRprotocolwithspecificprobesfortheendsofthe
adapters.TheqPCRassaymeasuresthequantityoffragmentsproperlyadapterligatedthatare
appropriateforsequencing.BasedontheqPCRquantification,librarieswerenormalizedto2nMand
thendenaturedusing0.1NNaOH.Clusteramplificationofdenaturedtemplatesoccurredaccordingto
manufacturersprotocol(Illumina)usingV2ChemistryandV2Flowcells(1.4mmchannelwidth).SYBR
Greendyewasaddedtoallflowcelllanestoprovideaqualitycontrolcheckpointaftercluster
amplificationtoensureoptimalclusterdensitiesontheflowcells.Flowcellswerepairedendsequenced
(2x101bpforWGSand2x76bpforWE)onGenomeAnalyzerIIs,usingV3SequencingbySynthesiskits
andanalyzedwiththeIlluminav1.3.4pipeline.Standardqualitycontrolmetricsincludingerrorrates,%
passingfilterreads,andtotalGbproducedwereusedtocharacterizeprocessperformancepriorto
downstreamanalysis.TheIlluminapipelinegeneratesdatafilesthatcontainthereadsandqualities.
Sequencedataprocessing
Datawereprocessedusingtwoconsecutivepipelines:
(1) Thesequencingdataprocessingpipeline,calledPicard,developedbytheSequencingPlatform
attheBroadInstitute,startswiththereadsandqualitiesproducedbytheIlluminasoftwarefor
alllanesandlibrariesgeneratedforasinglesample(eithertumorornormal)andproduces,at
theendofthepipeline,asingleBAMfile(http://samtools.sourceforge.net/SAM1.pdf)
representingthesample.ThefinalBAMfilestoresallreadswithwellcalibratedqualities
togetherwiththeiralignmentstothegenome(onlyforreadsthatweresuccessfullyaligned).
(2) TheCancerGenomeAnalysispipeline,alsoknownasFirehose,developedintheCancer
ProgramattheBroadInstitute,startswiththeBAMfilesforthetumorandpatientmatched
doi:10.1038/nature09837
normalsamplesandperformsvariousanalyses,includingqualitycontrol,localrealignment,
mutationcalling,smallinsertionanddeletionidentification,rearrangementdetection,coverage
calculationsandothers(seedetailsbelow).
SeveralofthetoolsusedinthesepipelinesweredevelopedjointlybytheBroadsSequencingPlatform,
MedicalandPopulationGeneticsProgramandtheCancerProgram(additionaldetailsregardingpartsof
thepipelinefocusedongermlineevents,alsousedformedicalandpopulationgenetics,willbe
describedelsewhere;DePristoetal.,inpreparation).
Thesequencingdataprocessingpipeline
WegeneratedaBAMfileforeachsampleusingthesequencingdataprocessingpipeline,knownas
Picard(http://picard.sourceforge.net/;FennelT.etal.,unpublished).Picardconsistsoffoursteps
(brieflydescribedbelow):(1)recalibrationofbasequalities,(2)alignmenttothegenome,(3)
aggregationoflaneandlibrarydata,and(4)markingofduplicatereads.
(1)Basequalityrecalibration
EachbaseisassociatedwithaPhredlikequalityQscore2representingtheprobabilitythatthebasecall
iserroneous.TheQscorerepresents10*log10(Probabilityoferror),roundedtoanintegervalue.In
ordertomakesurethatQ30basesindeedhavea1ina1000chanceofbeingwrongweusedaGATK
tool(http://www.broadinstitute.org/gatk)thatempiricallyrecalibratesthequalitiesbasedonthe
originalQscore(generatedbytheIlluminasoftware),thereadcycle,thelane,thetile,thebasein
questionandtheprecedingbase.TheoriginalqualityscoresarealsokeptintheBAMfileintheread
levelOQtag.
(2)Alignmenttothegenome
AlignmentisperformedusingMAQ3[http://maq.sourceforge.net/]totheNCBIHumanReference
GenomeBuild36.3.ThereadsintheBAMfilearesortedaccordingtotheirchromosomalposition.
UnalignedreadsarealsostoredintheBAMfilesuchthatallreadsthatpassedtheIlluminaqualityfilter
(PFreads)arekeptintheBAM.
(3)Aggregationoflaneandlibraryleveldata
MultiplelanesandlibrariesareaggregatedintoasingleBAMpersample.LanelevelBAMfilesare
combinedtolibrarylevelBAMfilesandthesearethencombinedtosamplelevelBAMfiles.TheBAM
filescontainreadgroupsthatrepresentthelibraryandlaneinformation.Informationregardingtheread
groupsappearsintheBAMheader(seetheBAMfilespecificationsin
http://samtools.sourceforge.net/SAM1.pdf).
(4)Markingofduplicatedreads
MolecularduplicatesareflaggedusingtheMarkDuplicatesalgorithmfromPicard
(http://picard.sourceforge.net/).Themethodidentifiespairsofreadsinwhichbothendsmaptothe
doi:10.1038/nature09837
exactsamegenomicpositionasbeingmultiplereadsofthesameDNAmoleculeandhencemarksallbut
thefirstasduplicates.
TheBAMfilesthatareproducedbythePicardpipelinearethendeliveredtodbGaP.Inthisstudywe
delivered52filesrepresenting26WGStumor/normalpairsandanadditional26filesrepresenting13
WEtumor/normalpairs.
TheCancerGenomeAnalysispipeline(Firehose)
TheCancerGenomeAnalysispipelineconsistsofasetoftoolsforanalyzingnextgenerationdata
representingtumorDNAsamplesandtheirpatientmatchednormalDNAsamples.Inordertobuilda
robustpipelinewedevelopedapipelineinfrastructureformanaginganalysisworkflows,calledFirehose
representingtheneedtohandlethefloodofnextgenerationandhighthroughputdata(VoetD.etal.,
unpublished).Firehosemanagestheinputfiles,theanalysistoolsandtheoutputfiles,andkeepstrack
ofwherethedatareside,whatneedstobeexecutedoneachfileandinwhatorder,andwhatis
currentlyrunning.Italsokeepstrackofversionsofthedataandmethodstoenablereproducingthe
analysisandresults.FirehoseusesGenePattern4asitsexecutionengine,whichisresponsibleforactually
runningthepipelinesandmodulesbasedonparametersandinputsfilesspecifiedbyFirehose.
Theanalysiscontainsthefollowingsteps(whicharedetailedbelow):
(1) Qualitycontrolensuringthatalldatamatchtheircorrespondingpatientandthatthereareno
swapsbetweentumorandnormaldataforthesameindividual.
(2) Localrealignmentofreadsreadsinregionsthatpotentiallyharborsmallinsertionsor
deletionsarejointlyrealignedtoimprovedetectionofindelsandtodecreasethenumberof
falsepositivesinglenucleotidevariationscausedbymisalignedtipsofreads.
(3) Identificationofsomaticsinglenucleotidevariations(SSNVs)candidateSSNVsaredetected
usingastatisticalanalysisofthebasesandqualitiesinthetumorandnormalBAMsthatmapto
thestudiedgenomicsite.Postfilteringofcandidatemutationsremovessystematicartifacts.For
WGSdata,weinterrogateeverypositionalongthegenome,andforWEdata,wesearchfor
mutationsintheneighborhoodofthetargetedexons(wherethemajorityofreadsarelocated).
Wealsoindicateforeveryanalyzedbasewhetheritissufficientlycoveredforconfident
identificationofpointmutations.
(4) Identificationofsomaticsmallinsertionsanddeletions(SINDELs)SINDELsaredetectedbyfirst
identifyingputativeeventslookingatthetumorBAM(withhighsensitivitybutalsoahighfalse
positiverate),andthenfilteringoutnoisyeventsandpotentialgermlineevents(usingthe
normaldata).
(5) Identificationofinterchromosomalandlargeintrachromosomalstructuralrearrangements
(SRs)candidaterearrangementsareidentifiedasgroupsofpairedendreadswhichconnect
genomicregionswithanunexpectedorientationand/ordistanceonthesamechromosomeor
fromdifferentchromosomes.Next,themethodappliesfilterstoremovegermlineandfalse
positivecalls.
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(6) Calculationofcoveragecalculatescoveragestatisticsacrossthegenomebrokenupaccording
todifferentgenomiczones.Thezonesincludeintergenicregions,exons,introns,untranslated
regions(UTRs),andpromoters.Eachzonewasfurtherdividedintoregulatorypotential(RP)
regionsandnonRPregions(seebelow).
(7) Mutationratecalculationcalculatesmutationratesbasedonthedetectedmutations(SSNVs
andSINDELs)andthecoveragestatistics.Mutations(andbases)arefurtherpartitionedinto
mutationcategoriessuchasmutationsin(i)CsorGsinCpGdinucleotides,(ii)AsorTs,(iii)other
CsorGs,(iv)mutationsthedisruptthegenessuchasframeshiftSINDELsandnonsense
mutationsand(v)inframeSINDELs.
(8) Identificationofsignificantlymutatedgenes,COSMICsites,orgenesetssignificantlymutated
genes/genesetsaredetectedbycomparingtheobservednumberofmutations(fromeach
category)acrossthesamplestotheexpectednumberbasedonthebackgroundmutationrates
andthecoveredbasesinallsamples.
(9) Identificationofsignificantlymutatedregionswithregulatorypotential(RPregions)RPregions
areidentifiedfromaUCSCtrack.Significantlymutatedregionsaredetectedbycomparingthe
observednumberofmutationsacrossthesamplestotheexpectednumberbasedonthe
backgroundmutationratesandthecoveredbasesinallsamples.
(10)Mutationimpactanalysisfunctionalimpact(FI)scoresforallnonsynonymouspointmutations
werecalculatedusingthexvar.orgwebsite(http://xvar.org/).Thisstepisnotyetautomatedand
wasperformedmanually.
(1)Qualitycontrol
MatchingIndividual
GenotypesweredeterminedfromSNP6.0arrays(wheneveravailableforthesample)usingtheBirdseed
algorithm5.Homozygousnonreferencesiteswerecomparedtoobservedbasesforeachlane
separately.Laneswhichhad<95%concordancetoSNParrayswereexcludedfromtheanalysis.
TumorandNormalMatching
Wedetectedtumor/normalswapsusingtwomethods.
(1) ForWGSdata,wesequencedtwolibrariesforeachsample(tumorandnormal).Theinsertsize
distributionisacharacteristicofthelibrary.Laneswithaninsertsizedistributionthatdoesnot
matchthedistributionoftheotherlanesgeneratedfromthesamelibraryareexcludedfromthe
analysis.
(2) ForWGSandWEdata,wecomparedthecopynumberprofileofeachlane(assessedusingthe
depthofcoverageinwindowsof100kbalongthegenome)totheprofiledeterminedbySNPor
aCGHarrays.Tumorlanesthatdonotmatchtheexpectedprofileornormallanesthatdeviate
fromtheexpectedflatprofilewereexcludedfromtheanalysis.
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Exclusionoftumorinnormalsamples
Bystudyingthecopynumberprofileofthenormallanes,wewereabletodetectvariouslevelsof
contaminationoftumorcellsinthenormalsamples(SupplementaryFig.10).Althoughpatientswith
frankplasmacellleukemiahadbeenexcludedfromthestudy,itwasnotedthatcontaminatedsamples
hadallbeenFicollpurified(potentiallyselectingforclonotypiccells)andhadbeendonatedbypatients
whohadreceivedmultiplecoursesoftreatmentforMM(andwhowerethereforeatincreasedriskfor
extramedullarydisease).Asaresultofthiscontamination,weexcluded4samplesthathadahighlevel
oftumorinnormalcontaminationandkept3sampleswithlowlevelcontaminationthatdidnotseem
toaffectourabilitytodetectsomaticevents.
(2)LocalRealignment
Thepurposeofthisstepistotakeintoaccount,andensuretheconsistencyof,alltheevidenceforan
indelavailablefrommultiplereadsmappedtothesameregion.Whenplacingreadsoneatatime(as
mostshortreadalignersdo,includingMAQthatwasusedforthisstudy)severalproblemsmayoccur
duetoindels:
(a) Analignermaynotbeconsideringplacementswithindelsatall.Forexample,MAQdoesnot
considerindelswithunpairedsequencingdata.Evenwithpaireddata,asinthisstudy,when
bothendsaremapped(potentiallysuboptimally)withoutanindel,MAQwillnotfurtherlook
forabetteralignmentwithanindel.
(b) Evenwhenindelsareconsidered,wheneveranindeloccursclosetotheendoftheread,the
aligneroftenprefersagaplessalignmentwithafewmismatchesattheendoftheread.
(c) Sequencingerrorsand/orvariationsinbasequalitiesinindividualreadsmayresultinindels
placedinconsistentlyatdifferentnearbylocations,especiallyinhighlyrepetitive,lowcomplexity
regions.
Often,thereisamixedsituationinwhichsomereadsplacetheindelcorrectly(whenitisinthemiddle
oftheread)whileafewmorereadsthatwouldhavethesameindelneartheendareplacedwith
mismatchesandnogap.Notcorrectingtheseplacementsreducestheabilitytodetectindelsand
increasesfalsepositiveindelandsinglenucleotidevariationcalls.
WeappliedtheIndelRealignermoduleinGATK(DePristoM.etal.,submitted)
[http://www.broadinstitute.org/gatk]thatperformsmultiplesequencealignmentofreadsnextto
putativeindelsitesidentifiedbyeitherthepresenceofanindelinatleastonereadorarunof
consistentconsecutivemismatches.
(3)Somaticsinglenucleotidevariationdetection
Mutationdetectionforbothwholegenomeandcapturedatawasperformedusingahighlysensitive
andspecificmethodwehavedevelopedinhousecalledmuTector(CibulskisK.etal.,inpreparation).In
brief,muTectorconsistsofthreesteps.
(1) Preprocessingthealignedreadsinthetumorandnormalsequencingdata.Inthisstepweignore
readswithtoomanymismatchesorverylowqualityscoressincetheserepresentnoisyreads
thatintroducemorenoisethansignal.
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(2) Astatisticalanalysisthatidentifiessitesthatarelikelytocarrysomaticmutationswithhigh
confidence.ThestatisticalanalysispredictsasomaticmutationbyusingtwoBayesianclassifiers
thefirstaimstodetectwhetherthetumorisnonreferenceatagivensiteand,forthosesites
thatarefoundasnonreference,thesecondclassifiermakessurethenormaldoesnotcarrythe
variantallele.InpracticetheclassificationisperformedbycalculatingaLODscore(logodds)and
comparingittoacutoffdeterminedbythelogratioofpriorprobabilitiesoftheconsidered
events.Forthetumorswecalculate
P(observeddataintumor|siteismutated)
LODT = log10
,andforthenormal
P(observeddataintumor|siteisreference)
P(observeddatainnormal|siteisreference)
LODN = log10
.
P(observeddatainnormal|siteismutated)
Sinceweexpectsomaticmutationstooccuratarateof~1inaMb,werequire
LODT > log10 ( 0.5 10 6 ) 6.3 whichguaranteesthatourfalsepositiverate,duetonoise
inthetumor,islessthanhalfofthesomaticmutationrate.Inthenormal,notindbSNP
sites,werequire LODN > log10 0.5 10 2 2.3 sincenondbSNPgermlinevariantsoccur

roughlyatarateof100inaMb.Thiscutoffguaranteesthatthefalsepositivesomaticcall
rate,duetomissingthevariantinthenormal,isalsolessthanhalfthesomaticmutation
rate.
(3) Postprocessingofcandidatesomaticmutationstoeliminateartifactsofnextgeneration
sequencing,shortreadalignmentandhybridcapture.Forexample,sequencecontextcancause
hallucinatedalternateallelesbutoftenonlyinasingledirection.Therefore,wetestthatthe
alternateallelessupportingthemutationsareobservedinbothdirections.
AsmuTectorattemptstocallmutationsitalsogeneratesacoveragefile(inawigglefileformat6,which
indicatesforeverybasewhetheritissufficientlycoveredinthetumorandnormaltobesensitive
enoughtocallmutationsseesectiononcoveragebelow).Wecurrentlyusecutoffsofatleast14reads
inthetumorandatleast8inthenormal(thesecutoffsareappliedafterremovingnoisyreadsinthe
preprocessingstep).
AccuracyofmuTector
Inordertoestimatethespecificityofthemethod,weselectedasemirandomsetof100somaticsingle
nucleotidevariationsincodingexons.Initialselectionwasrandom,butforeachgenewithmorethan
onemutation,otherobservedvariantswereselectedforgenotyping.Weattemptedtodesign
Sequenomgenotypingassaysforthese100mutationsandassaydesignwassuccessfulfor92.87of
these92mutationswerevalidatedassomaticmutations(SupplementaryTable4),yieldinganestimated
truepositiverateof95%(95%CI,88%98%).All5mutationsthatfailedtobeconfirmedwerenot
presentinthetumor.Largervalidationeffortsinotherdatasetshaveconsistentlyestimatedthetrue
positiverateat~90%.
doi:10.1038/nature09837
Effectofcoverageonmutationdetectionandsensitivity
SensitivityismorechallengingtoassessthanFPrate,owingtothelackofasetofgroundtruth
mutations.ThemutationratesofNRASandKRASweretowardstheupperendoftherangeoftheir
publishedprevalenceinMM,implyinggoodsensitivityinthissinglecase.Sensitivityisnotuniformforall
genes,however,andisinfluencedtoalargeextentbyexoniccoverage.This,inturn,isinfluencedbyGC
content(withlowercoverageinmoreGCrichareas,oftenduetodifficultyinperformingalignmentof
reads)and,inthecaseofWES,bywhetherexonsweretargetedbythebaitandwhetherthebaitwas
successfulincapturingtheprey(SupplementaryFig.11).Nonuniformcoverageresultsinreduced
sensitivityforsomegenes(SupplementaryFig.12).Thus,forexample,ourpowertodetectamutation
witha20%frequencyassignificantwouldbegreaterthan0.8forthemajorityofgenes,assuming
uniformcoverage(SupplementaryFig.12a).However,thenonuniformcoverageresultsinagreater
than0.8powerforonlyabouthalfthegenes(SupplementaryFig.12b).Inabout17%ofgenes,the
powertodetectsignificantmutationsisreducedbymorethan80%owingtopoorcoverage
(SupplementaryFig.12c).
Toattempttobetterdefineoursensitivity,weexaminedthesampleforwhichwehadperformedboth
WESandWGS(SupplementaryFig.2).Wefirstexcludedfalsepositivemutations(bymanualreviewof
supportingreads).WethenassessedthenumbersofmutationsidentifiedbymuTectorinWESalone,in
bothWESandWGS,andinWGSalone.Thissuggestedsensitivitiesof67%forWESand88%forWGS.
ReducedsensitivityinWESwasentirelyduetoanabsenceoftargetingbythebaitset.Whenanalysisis
restrictedtotargetedregions,thesensitivityofmuTectorinWESisthesameasthatinWGS(88%).
Annotationofmutations
(4) Eachmutationwasannotatedwithadditionalinformationregardingthefollowingparameters.
(1)Thegenomiczoneexon,intron,promoter,UTR,intergenicregion(IGR).
(2)Positioninprotein.
(3)Mutationtypenonsynonymous,silent,splicesite.
(4)Aminoacidchange.
(5)Proteindomain.
SomaticmutationsarelistedinSupplementaryTable3.
(4)Detectionofshortinsertionsanddeletions
Indelcallingoperatesonlocallyrealigneddata(seeabove)andconsistsoftwosteps:(i)callingputative
indelevents(withhighsensitivity);(ii)filteringtheinitialputativecalls.
Theindelcallingstepisperformedbycountingindeleventsinreadsateverylocus(inthetumorBAM)
andapplyingbasiccutoffsonstatisticssuchase.g.theindelallelefraction(fractionofindelcontaining
reads).Thesehighsensitivitycallsarefurtherfilteredinthenextstepbyexaminingadditional
characteristicsofthealignmentsintheneighborhoodsuchastheaveragenumberofmismatchesinthe
reads,distributionofbasequalitiesandothers.Theeventsarefurtherannotatedasgermlineorsomatic
doi:10.1038/nature09837
10
basedonwhetheranyevidencefortheeventatthesamelocusisobservedinthenormaldata.Further
detailswillbeprovidedelsewhere(Sivachenkoetal.,inpreparation).
Indelvalidation
WeattemptedtodesignSequenomassaysforallcalledindels.Itwaspossibletodesignassaysfor
10/23.Ofthese,80%(95%CI4497%)werepositivelyvalidated.Othersmallindelsweresubjectto
manualreviewofsupportingreadsusingtheIntegrativeGenomicViewer(IGV;RobinsonJ.etal.,in
preparation)andfalsepositivecallsexcluded.
ValidatedindelsarelistedinSupplementaryTable4.
(5)Identificationofchromosomalrearrangements
Rearrangementdetection
Fordetectionofchromosomalrearrangements,wehavedevelopedthedRangeralgorithm(Lawrence
M.S.etal.,inpreparation).Thefirststepofthealgorithmisidentificationofgroupsofreadpairsinthe
tumorthatarediscordant,i.e.mappedtolocationsthataredistantfromeachotherinthegenome,
eitherondifferentchromosomesorfartherapartonthesamechromosomethanwouldbeexpected
fromtheinsertsizedistributionofthefragmentlibrary(whichistypically400+/50bp).Forintra
chromosomalpairs,weuseacutoffof600bpforpairsofstandardorientation(i.e.onereadonthe
forwardstrandandtheotherreadonthereversestrandandmappedtoalaterpositiononthe
chromosome),and200bpforpairsofanomalousorientation(anyotherconfiguration,includingboth
pairsonthesamestrand).Eachsuchsetofdiscordantpairscorrespondstoapotentialrearrangement
event.Foreachset,thematchednormalisexaminedtocounthowmany(ifany)readpairsinthe
normalalsosupporttheevent(andthusidentifyitasagermline,asopposedtoasomatic,event).
Additionally,apanelofnormalsisexamined,toidentifygermlineeventsthatmayhavealowdetection
rateduetopoormapabilityorotherfactors.Next,aseriesoffilteringmetricsarecomputedforeach
potentialrearrangement.
(1) Thefractionofreadsinthevicinityofeachendpointthathavemappingqualityofzero.
(2) Thenumberofdistinctkindsofdiscordantpairsinthevicinityofeachendpoint.
(3) Thestandarddeviationofthestartingpositionsofthesupportingreads.
Thesefilteringmetricsarecombinedintoanoverallqualitymeasure,where0indicatesalikelyartifact
and1indicatesalikelytrueevent.Finally,ascoreisassignedtoeachrearrangementbymultiplyingthe
numberofsupportingreadstimesthequality.
RearrangementswereannotatedaccordingtotheRefSeqdatabase.Foreachrearrangement,each
endpointwasannotatedastowhetheritoccurredinanintergenicregionoragene,and,ifthelatter,
whethertheendpointwasinanintron,aUTR,oranexon.Forrearrangementswithbothendpoints
locatedingenes,therearrangementwasfurtherannotatedastowhetheritcouldpotentiallycausea
genefusion(eitherinframeoroutofframe).
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Allreportedrearrangementswerefurtherfilteredfortheirabilitytodisruptproteincodingofgenes
(SupplementaryTable3).Thisisincontrasttotheirabilitytoaffectnormaltranscriptlevel,whichis
hardertopredictwithconfidence.Thus,reportedrearrangementsincludethefollowing:deletionsand
tandemduplicationsaffectingatleastpartofonecodingexon,butnotallcodingexonsinagene;
inversionswithabreakpointbetweentheATGandstopcodon,butnotlimitedtoasingleintron;and
translocationswithabreakpointbetweentheATGandstopcodon.Itshouldbenotedthatthisfiltering
willexcludemanyoftherecurrentIgHtranslocations,inwhichthebreakpointofthetargetgeneoften
liesupto1Mbawayfromthetranscriptionalstartsite(bycontrast,WHSC1mutationswerefrequently
found,astheirbreakpointoftenlieswithintheWHSC1gene).
Assemblyofbreakpointsequences
Foreachpredictedrearrangement,thenucleotidelevelstructureofthechimericjunctionwas
determinedusingourBreakPointeralgorithm(DrierY.etal.,inpreparation).Briefly,thealgorithmlooks
forreadsthatmappedtoeithersideoftherearrangementandhadapairmatethatthealignerwas
unabletoalign.TheseunmappedpairmatesarethensubjectedtoamodifiedSmithWaterman
alignmentprocedurewiththeabilitytojumpbetweenthetworeferencesequencesatthebestfitting
point.
Rearrangementvalidation
LargescalePCRvalidationinotherprojectsyieldedaTPrateof90%forrearrangementswithatleast8
supportingreads,85%forrearrangementswithatleast4supportingreads,and80%forrearrangements
withatleast2supportingreads.Toincreaseourspecificity,weperformedmanualreviewofsupporting
readsforallreportedrearrangements(i.e.thosepredictedtodisruptproteincodingseeabove).It
shouldbenotedthat,comparedtoPCRvalidation,thedRangerfalsepositiverateasassessedbymanual
readreviewwasverysimilarforrearrangementswithhighnumbersofsupportingreads,butmuch
higherforrearrangementswith2supportingreads(themajorityofcalledrearrangements).Itisthus
likelythatfilteringbymanualreviewofsupportingreadsresultsinhigherspecificitybutlowersensitivity
callsthanvalidationbyPCR.
(6)Calculationofcoverage
Forpurposesofdeterminingthesignificanceofobservedmutationpatterns,abasewasdefinedas
beingcoverediftherewereatleast14readsthatoverlappedthepositioninthetumorand8readsin
thenormal.ThenumberofcoveredbaseswastabulatedacrossthegenomesoftheWGSsamplesand
theexomesoftheWEsamples.
Genomicterritorywasbrokendownaccordingtoaseriesofcriteria.First,thegenomewasdividedinto
genesandintergenicregions(IGR),accordingtotheRefSeqdatabase.Then,withineachgene,the
transcribedsequencewasdividedintoexons,introns,and5and3untranslatedregions.Furthermore,
apromoterregionwasimputedtoexistinthe3kbregiondirectlyupstreamfromthe5UTR.
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Tocapturethefactthatthegenomecontainsmanyregionsthatarehighlyrepetitiveorotherwise
problematic,genomicterritorywasfurthersplitintogoodandbad.Thiswasdoneempiricallyusing
theobservedcharacteristicsofsequencedatafromanormalsample(MM0319).Aregionwascalled
badifitcontainedoneormoreofthefollowing.
(1) Ahighproportionofreadswithmappingqualityequaltozero,whichistheconventionthatthe
alignerprogramMaqusestoindicatethatthereadcouldhavebeenplacedatanyofanumber
ofequivalentlocationsinthegenome,andthatspecificpositionwaschosenrandomly.This
indicatesahighlyrepetitivesequencewherevariantcallsarenecessarilyunreliable.
(2) Alargenumberofdifferentkindsofdiscordantpairs.
(3) Anextremelyhighconcentrationofnonreferencebases.
(7)Backgroundmutationratecalculation
Toaccountforthefactthatcertainbasecontextsareknowntohaveincreasedmutationrates,e.g.C
residuesinCpGdinucleotides,wecalculatedseparatecontextspecificmutationratesfortransitions
andtransversionsaffectingCpGs,otherCorG,orATbasepairs.Wealsocalculatedtheserates
separatelyforthevariouszones(e.g.exonvs.intron,goodvs.bad).Althoughthemutationratein
samplesfromrelapsedpatientswashigherthaninsamplesfromnewlydiagnosedpatients,the
differencewasnotsignificantlydifferent(SupplementaryFig.13).
Wecomparedmutationratesintheintronsofcommonlyexpressedgenestothoseinrarelyexpressed
genesinMM.WeusedtheMMRCexpressiondataset(seebelow)todividethegenesofthegenome
intosevencategories:(1)expressedin>75%ofmultiplemyelomasamples;(2)expressedin5075%;(3)
expressedin2550%;(4)expressedin525%;(5)expressedinatleastonesampleandlessthan5%;(6)
noexpressiondetectedinanysample;and(7)noexpressiondata.Wethencomputedintronicsomatic
mutationratesinthese7categories.Wechosetoexcludeintronicratesincategory(6)becausethiswill
includepoorlyperformingprobesetsandubiquitouslyexpressedgeneswhosebasalexpressionlevels
areverylowandundetectablebyAffymetrixprofiling(e.g.transcriptionfactors).Wealsoexcluded
intronicratesincategory(7),forobviousreasons.ThesedataareshowninFig.1a.
(8)Identificationofsignificantlymutatedgenes
Foranalysisofmutationdataandidentificationofsignificantlymutatedgenesandextragenicelements,
wehavedevelopedanalgorithmcalledMutSig(Lawrenceetal.,inpreparation),basedinparton
methodswehavepublishedelsewhere7,8.Inbrief,wetabulatethenumberofmutationsandthe
numberofsuccessfullysequenced(i.e.covered)basesforeachgene.Thecountsarebrokendownby
mutationcontextcategory(CpG,otherC:G,A:T).Foreachgene,wecalculatetheprobabilityofseeing
theobservedconstellationofmutationsoramoreextremeone,giventhebackgroundmutationrates
calculatedacrossthedataset.Thisisdonebyconvolutingasetofbinomialdistributions,asdescribed
previously9.ThispvalueisthenadjustedformultiplehypothesesaccordingtotheBenjaminiHochberg
procedureforcontrollingFalseDiscoveryRate(FDR),obtainingaqvalue.
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Weextendedoursignificanceanalysisbeyondsinglegenesbylookingatgenesets.Wedownloadedthe
listofcanonicalpathwaysusedinGeneSetEnrichmentAnalysis(GSEA).Thislistcontains639genesets
correspondingtoknownpathwaysorgenefamilies.Weconsideredallpathwaysthatcontainedatleast
onegeneinthesetofgenestargetedinWEsequencing,alistof616genesets.Foreachgeneset,we
tabulatedthenumberofmutationsinthegeneset(i.e.mutationsoccurringinanycomponentgene),as
wellasthetotalnumberofcoveredbasesinallgenesinthegeneset.Countswerebrokendownby
basecontextcategoryasinthesinglegeneanalysis.Apvaluewascalculatedforeachgenesetas
above,andthenaqvaluewascomputedtoaccountforthelistof616hypotheses.
(9)Identificationofsignificantlymutatedregionswithregulatorypotential
Inadditiontocataloguingallpointmutations,smallindels,andlargerrearrangementsthatwould
disruptproteincodingregions,wewantedtoassesswhetheritwaspossibletodetectnoncoding
mutationsinregulatoryregions(promoters,enhancers,silencers,etc.).Thegenomewideannotationof
theseregionsisverylimitedcomparedtocodingregions,soweadoptedthefollowingstrategy(seealso
SupplementaryFig.9).
(1) Definegenomewideregionsofregulatorypotential(RPregions).
(2) AssessthenumbersofmutationsseenineachRPregionforsignificanceandcorrectformultiple
hypothesistesting.
(3) Performfilteringandvalidation.
Eachofthesestepsisoutlinedbelow.
DefinitionofRPregions
WedownloadedtheregulatorypotentialtrackfromtheUCSCbrowser10,11
(http://hgdownload.cse.ucsc.edu/goldenPath/hg18/regPotential7X/).SeeKolbeetal.11forfulldetailsof
howthisRPscorewasdefined,butbriefly,themethodinvolvedtrainingMarkovmodelsonthreeway
(human/mouse/rat)alignmentsofexperimentallydefinedregulatoryregionsandthreewayalignments
ofancestralrepeatregions,representingneutralDNA.Themodelwasthenappliedtoagenomewide
threewayalignmentandtheRPscorecalculatedfromthelogratiosofthetransitionprobabilitiesofthe
twoMarkovmodelsatanygivenposition.
TheRPscoresasdownloadedrepresentbasetobasescores.TodefineourRPregions,weprocessedthe
scoresbypassingaslidingwindowof100bpovereachchromosome,movedatincrementsof10bp,
andtakingtransitionsbetweenzeroandanynonzeroscoretobetheboundaries.Thisprocedureyielded
alistofatotal2.38millionRPregionsfortheentirehg18genome.
WecomparedthebackgroundmutationratesintheRPandnonRPregionsfromWGS.Wefoundlower
observedsomaticmutationratesinRPregionscomparedtononRPregions(SupplementaryFig.14).
Thiseffectpersistedevenwhencontrollingforbasecontext,withthedifferencebeingseenforeach
individualbasecontextcategory.
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AssessingRPregionsforsignificance
ForeachRPregion,wecalculatedthenumberofmutationsobservedacrossthepanelof23patients
sequencedbyWGS,andthenumberofcoveredbases.WeperformedapvaluecalculationandanFDR
correctionforthe2.38millionhypotheses.ThisyieldedalistofRPregionsrankedbysignificancelevel.
Filteringandvalidation
Wenotedthatmanyofthetopregionsweresituatedinthevariousimmunoglobulinloci(IgH,Ig,and
Ig),knowntobetargetedbysomatichypermutation.Wealsoobservedaregionspanningthe
promoter,firstnoncodingexon,andpartofthefirstintronofBCL6,anotherregionknowntoundergo
somatichypermutation12.Thisidentificationofknownregionsofsomatichypermutation,shownin
SupplementaryTable9,wasencouraging,butwewerekeentoidentifymutationsinregulatoryregions
thatmaybedriversofMMpathogenesis.Wethereforerepeatedtheanalysisfollowingmaskingof
knownregionsofsomatichypermutation.Thisyielded116regionswithq<0.25.Weexcluded37
regionsbecauseallofthemutationswereconfinedtoasinglesample.Wefurtherexcludedoneregion
thatincludedthefirstcodingexonofNRASandinwhichall5mutationswerenonsynonymouscoding
mutationswithinthisexon.
Wethenperformedmanualreviewofthesupportingreadsfortheremainingregions.Thisexcluded60
regions,leaving18potentialsignificantlymutatedregulatoryregions(Table2).11/18oftheseregions
weresubjectedtovalidationbyPCRandSangersequencing(PCRprimersandconditionsareshownin
SupplementaryTable11).All11testedsetsofmutationswerevalidatedastruepositives,confirming
highspecificityoffilteringbymanualreview.
(10)Assessmentofthefunctionalimpactofmutations
Foreachmutation,weobtainedanestimateofthelikelihoodthatthemutationimpactstheprotein
functionally,usingthexvar.orgwebsite(http://xvar.org;B.Reva,personalcommunication)tocalculate
aFunctionalImpact(FI)score13.WecomparedthedistributionoftheseFIscoresacrossthemutations
foundinsignificantlymutatedgenesvs.allothergenesbytheKolmogorovSmirnovtest(Fig.1b).To
excludethepossibilitythatthedifferencewasduetomutationsinanysinglehighlyconservedgene,we
repeatedthecalculation,sequentiallyleavingouteachgene(andbothgenesforNRASandKRAS).For
eachleaveoneouttest,thedifferenceremainedsignificant.Totestwhetherthesignificantdifference
wasduetothesetofgenesorsetofmutationswithinthosegenes,wegeneratedFIscoresforall
possiblemutationsinthe10significantlymutatedgenesandcomparedthisdistributiontotheFIscores
fortheobservedsetofmutationswithinthosegenes.TheobservedFIscoresweresignificantlyhigher
thanthenulldistributionofnullFIscores,suggestingthatthemutationsthemselvesweretargeting
functionalregionswithinthegenes(datanotshown).
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Othermethods
Publiclyavailableexpressionandcopynumberdatasets
Twoexpressiondatasetswereused.One,fromtheUniversityofArkansas(n=414),wasderivedfrom
newlydiagnosedpatientswithMM14.Thesecond,fromtheMultipleMyelomaResearchConsortium
(MMRC;n=304),wasderivedfromamixofnewlydiagnosedandpreviouslytreatedpatientswithMM.
BothwereobtainedusingtheAffymetrixU133Plus2.0arraysandbothareavailablefordownloadfrom
theMultipleMyelomaGenomicsPortal(MMGP;http://www.broadinstitute.org/mmgp).Thecopy
numberdataset(n=254)isalsofromtheMMRCandisderivedfromasubsetofthesamepatients
contributingtotheexpressiondataset.ItwasobtainedusingtheAgilent244KaCGHplatform.Itis
availablefordownloadfromtheMMGP.
Genesetenrichmentanalysis(GSEA)forFAM46Ccoexpressedgenes
GSEAwasperformedusingversion2.06(http://www.broadinstitute.org/gsea/downloads.jsp).Thegene
listwasconstructedbyrankingofPearsoncorrelationofexpressionwithFAM46C(probeset
226811_at).Thetesteddatasetswerederivedfromthe639C2CanonicalPathways
(http://www.broadinstitute.org/msigdb/index.jsp).Theywerefilteredforsizeaccordingtothedefault
settings(range15500),yielding395genesets.Pvalueswereobtainedbypermutation(n=100)and
adjustedformultiplehypothesesaccordingtotheBenjaminiHochbergprocedureforcontrollingFDR,
yieldingaqvalue.
Outliersumstatistic(OSS)calculation
AvariantoftheOSS15wasused.ForcalculationoftheOSS,samplesaredividedintotwogroupsandthe
OSScalculatedonametricinoneofthegroups.Inthiscase,itwasreasonedthatitwouldbe
informativetolookforoutliereventsoccurringinMMsampleslackinganobviousdriver.Sampleswere
thereforesegregatedbasedonpresenceorabsenceofarecurrentIgHtranslocation(targetingoneof
CCND1,CCND3,FGFR3/WHSC1,MAF,orMAFB),forwhichexpressiondatacanprovideanaccurate
surrogate16.Thussegregated,theOSSwasappliedasdescribedforeachprobesetintheexpression
dataset.AstheOSSmaybedrivenbyboththelevelsofgeneexpressioninoutliersandbythenumber
ofoutliers,therankedlistofgeneswasprioritizedbyasecondmeasure.Forthis,apermutationtest
(n=1000)wasappliedandtheobservedOSScomparedtoanulldistributionofOSS.Notethatthis
proceduredoesnotyieldapvalue,owingtothesparsedistributionofoutliersinthedataset.
Nonetheless,itaffordedausefulprioritizationofpotentialdrivergenesandgeneswerefilteredfora
permutationscoreoflessthan0.05.Thetop20hitsareshowninSupplementaryTable12.HOXA9was
rankednumber3behindapseudogene(TSPY6P)andahypotheticalproteingene(LOC283352),sowas
prioritizedforfurtherinvestigation.
ThepatternofoutlierHOXA9expressioninMMisshowninSupplementaryFigure4a.Somefurther
explanatorycommentsareworthmakingaboutthisfigure.Differentnormalizationmethodswere
appliedtotherawmicroarrayimagesintheArkansasandMMRC/celllinedatasets(MAS5forArkansas,
doi:10.1038/nature09837
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robustmultiarrayanalysisRMAforMMRCandcelllines).Itislikelythatthisaccountsforapparent
differencesinHOXA9outlierexpressionvaluesbetweenArkansasandMMRC/celllinedatasets.
However,thefrequencyofoutlierswasthesame(10%)inboththeArkansasdatasetandtheMMRC
dataset.Thenormalizedoutlierexpressionvaluesspanaverywiderangeinbothdatasetsandsomeare
expressedonlyalittlehigherthanthelevelofnoise.Hencethesemaynotbeobviouswhenplotted.
However,qPCRofHOXA9(SupplementaryFig.4b;seebelow)showsubiquitousexpressionandthe
outliersarereliablydifferentiatedfromnonoutliersbythismethod.Ubiquitousexpressionof
transcriptionfactorsatalevelundetectablebymicroarraysappearstobeacommonevent(unpublished
observationsbasedonRNAsequencing).
ItwillbeimportanttoassesscorrelationbetweenHMTmutationstatusandHOXA9expression.
However,thereisinsufficientpowertoinvestigatethisrelationship.Nevertheless,wewould
hypothesizethathistonemodifyinggenemutationwoulddrivebiallelicexpression,whichisassociated
withnonoutlierstatus(SupplementaryFig.4c).Inthesecases,wedoseeabnormalH3K27Me3
enrichment(Fig.3a),whichisnegativelycorrelatedwithexpressionlevels(Fig.3b).Asnotedinthemain
text,outlierstatusisassociatedwithmonoallelicexpression(SupplementaryFig.4c),whichsuggestsa
cisactivatingmechanisminthesecases.
FocalamplificationsoftheHOXAlocusareseeninabout5%ofpatients.Someoftheseareassociated
withoutlierexpressionstatusofHOXA9.Thereare,however,sampleswithoutlierexpressionandno
amplificationandviceversa.WewouldspeculatethatsmallincreasesofHOXA9achievedbya1or2
copynumbergainmaybebeneficialtoMMcells(wedonothavesufficientRNAfromoutliersamplesto
testthisrelationship),butthatthiswouldbeinsufficienttodriveveryhighlevelsofexpression.This
phenomenonwouldaccountforsampleswithamplificationbutnotoutlierexpression.Ontheother
hand,acisactivatingeventmightbesufficienttodrivehighexpressionandwouldnotrequirean
amplification,accountingforthosesampleswithveryhighexpressionbutlackinganamplification.For
thoseinwhichbothphenomenaareseen,onemightexpectthataproportionofthesampleswithacis
activatingeventwouldsubsequentlyamplifytheaffectedregionasthiswouldprovideafurther
selectiveadvantage.
Itwillalsobeimportanttoassesstherelationshipbetweenhistonemodifyinggenemutationsandthe
histonemethylmarks.Thisisbeyondthescopeofthisstudyaswedonotpossesstherelevantsamples
toassessthelatterinthepatientswhoseDNAwassequenced.Conversely,establishingmutationstatus
inMMcelllines,inwhichwedohavedataonhistonemethylationstatus,isnotpossiblewithcurrent
mutationdetectionalgorithmsastheseareunabletodifferentiateprivateSNPsfromsomaticmutations
intheabsenceofmatchednormalDNA.
Celllines
ThefollowingMMcelllineswereusedinthestudy:H929,INA6,JIM3,KMS11,KMS12BM,KMS12PE,
L363,MM.1S,OPM2,OCIMy5,OCIMy7,SKMM1,U266,andXG6.ForallelespecificexpressioninAML,
thecelllineMOLM14wasused.AllcellsweregrowninRPMI1640media(FisherScientific)
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supplementedwith10%fetalbovineserum(SigmaAldrich).MediaforINA6andXG6were
supplementedwith2ng/mlIL6(RandDSystems).Cellsweregrownat37oCin5%CO2.
RTPCR
Asoutlinedinthemaintext,astatisticallysignificantcollectionofmutationswasdiscoveredamongst
membersoftheextrinsicclottingpathway.RTPCRwasusedtoassesswhetherthesecoagulation
factorswereexpressedinMMcelllines.F5expressionwasnotassessed,asF5isknowntobeexpressed
incellsofthelymphocyticlineage.RNAwasextractedusingaminiprepkit(Qiagen).DNasedigestion
wasperformedifgenomicDNAbandssubsequentlyprovedproblematic.cDNAwasproducedusinga
firststrandsynthesiskit(Promega)andPCRwasperformed.Forwardandreverseprimersweredesigned
todifferentexonssothatcDNAandgenomicDNAbandscouldbedistinguished.Primersequencesand
conditionsofthereactionsareshowninSupplementaryTable13.PositivecontrolcDNAwasobtained
fromdermalfibroblasts(F3)orwholeliverextract(theremainder).AnLDHAcontrolwasincludedto
ensureapproximatelyequalloadingofcDNA.ResultsareshowninSupplementaryFig.8.
AssessmentofHOXA9proteinexpression
ImmunoblottingwasperformedusinganantiHOXA9antibody(Millipore).Thecorrectbandsizewas
ascertainedbyreferencetopublisheddatawiththesameantibody17andbyretroviraloverexpressionof
HOXA9.Anantibodyagainstactin(CellSignalingTechnology)wasusedasaloadingcontrol.
AssessmentofHOXA9mRNAexpression
RNAwasextractedfromcellsusingaminiprepkit(Qiagen)accordingtomanufacturersinstructions.
FirststrandsynthesisandrealtimePCR(RTqPCR)wereperformedusingaonestepkitona7900
thermalcyclerandaninventoriedprobeprimerset,Hs00365956_m1(allAppliedBiosystems)usingthe
CTprotocol,accordingtothemanufacturersinstructions.actin(AppliedBiosystems)wasusedas
anendogenousloadingcontrol.Forassessmentofbasalexpressionlevels,expressionwasreported
relativetothatinthelowestexpressingcellline(JIM3).Forassessmentofknockdown,expressionwas
reportedrelativetothatincellsinfectedwiththecontrolhairpin,shLuc.Asaberrantpatternsof
H3K27Me3enrichmentwerealsoseeninthepromotersoftheHOXA9flankinggenes(HOXA7and
HOXA10),geneexpressionofthesewasassessedbythesamemethod.However,HOXA7andHOXA10
expressionwasfoundtobecompletelyabsent(datanotshown).
Chromatinimmunoprecipitation(ChIP)assayforhistone3lysine27
trimethyl(H3K27Me3)promoterenrichment
ChIPwasperformedasdescribed18(also,Adlietal.,inpreparation).~0.51.0x107cellswerecrosslinked
with1%formaldehydefor10minutesat37oC.Cellswerequenchedwithglycinefor5minutesand
washedtwicewithicecoldPBS.Cellpelletswereresuspendedin500loflysisbuffer(1%SDS,10mM
EDTA,50mMTrisHCl,ph8.1)andincubatedonicefor10minutes.Thelysatewasdilutedbyadding500
lChIPdilutionbuffer(0.01%SDS,1.1%TritonX100,1.2mMEDTA,16.7mMTrisHCl,ph8.1).The
doi:10.1038/nature09837
18
chromatinwassonicatedfor5minutesusingaBranson250sonicatorat40%poweramplitude(pulses:
0.7secondson,1.3secondsoff).Chromatinwasthenimmunoprecipitatedovernightinatotalvolumeof
10mlChIPdilutionbuffercontainingproteaseinhibitorcocktails(Roche)with10gH3K27Me3
(Millipore).EnrichmentwasdetectedattheHOXA9promoterbySYBRGreenqPCR(primers:
CGCTCTCATTCTCAGCATTGsense;CCACGCTTGACACTCACACTantisense).
HOXA9knockdown
shRNAconstructs
shRNAsclonedintovectorpLKO.1wereobtainedfromTheRNAiConsortium(TRC),viaOpenBiosystems
(http://www.openbiosystems.com/RNAi/shrnaLibraries/).shRNAshavebeennamedaccordingtothe
firstbasetargetedinthehumancDNA.AshRNAtargetingluciferase(shLuc)wasusedasanegative
control.ForGFPcompetitionexperiments,thepuromycincassetteofpLKO.1wasreplacedbyeGFPby
cloningintotheBamHI/KpnIsites.
Generationofvirusforknockdown
ViruswasproducedaccordingtoTRCprotocols
(http://www.broadinstitute.org/rnai/public/resources/protocols).Briefly,HEK293Tcellswereco
transfectedwithshRNAplasmidandpackagingplasmidscontaininggag,tat,rev,andVSVGgenes.Virus
washarvestedat40hourspostinfection,passedthrough0.45mfilters,andusedfreshforshRNA
infection.
AssessingdegreeofHOXA9knockdown
Cellsat4x106/mlwereinfectedin6welldishes.2x106cellsperwellwereplatedwith2mlfreshvirus
andPolybrene(hexadimethrinebromide;SigmaAldrich)toafinalconcentrationof8g/ml(1g/mlfor
XG6,whichwassensitivetohigherconcentrations).Spinoculationat750gfor30minuteswas
performed.Mediawasreplacedat24hourspuromycindihydrochloride(SigmaAldrich)at2.5g/ml.
Infectionefficienciesinexcessof80%wereconfirmedbycomparingviablecellcountsinpuromycin
selectedversusnonselectedcultures(mockinfectedcellsensuredefficacyofpuromycin).RNAwas
obtained72hourspostinfectionandcelllysateswereobtainedat120hourspostinfection,priortoany
hairpineffectsonviabilitybeingobserved.Residualcellcultureswerecontinuedforupto2weeksto
ensurecorrelationofhairpineffectswitheffectsobservedinphenotypicassays.HOXA9mRNAand
proteinwasassessedasdescribedabove.DegreeofknockdownwasdeterminedbycomparingHOXA9
expressioninresponsetoinfectionwithaparticularshRNAversusHOXA9expressionincellsthathad
beeninfectedwithshLuc.
AssessingeffectsofHOXA9knockdown
Cellswereplatedinreplicatesin96wellplateformatwithfreshvirusatmultipletitersandPolybreneto
afinalconcentrationof8g/ml(1g/mlforXG6).Spinoculationat900gfor90minuteswasperformed.
Mediawasthenimmediatelyrefreshed.Cellswereassessedat72hoursonaBDLSRIIflowcytometer
doi:10.1038/nature09837
19
(BectonDickinson).Deadcellswereexcludedusingaforwardscatter/sidescattergatingstrategythat
hadbeendeterminedinapreviousoptimizationexperimentusing7AAD(BectonDickinson).Proportion
ofinfectedcellswasassessedbymeasuringGFPonasinglechannel.Foreachcellline/shRNA
combination,replicatesfromasingletiterwereselectedforfurtherassessment.Thetiterselectedwas
thatwhichachievedclosestto50%GFP+cellsat72hours.GFP+proportionwasthenmeasuredevery96
hoursfortwoweeksandexpressedrelativetotheproportionat72hours(designatedday0;Fig.3cand
SupplementaryFig.6).Inaseparateconfirmatoryexperiment,cellswereplatedin96wellformatas
describedaboveusingtheminimalviraltiterthathadbeenshowntoachieve80%infectionefficiencyat
72hours.Cellviabilitywasthenassessedat72hours(baseline)usingCellTiterGlo(Promega)andattwo
subsequenttimepoints(SupplementaryFig.5anddatanotshown).
WenotethatthelevelsofmRNAandproteinknockdowndonotcorrelatewell.Thisisafrequently
observedphenomenonandthelevelsofproteinknockdownarethemoreimportanttoconsider19.
Nevertheless,thereremainssomedisconnectbetweenthelevelsofproteinknockdownandthe
severityofthephenotype.Eventhoughmanyofthesehairpinshavebeenpreviouslyvalidatedfor
specificeffectsinMLLleukemia,includingarescueexperiment17,itispossiblethatsomeexhibitan
elementofofftargettoxicity.Nevertheless,itishighlyunlikelythatalloftheeffectsofallofthehairpins
arenonspecific.Importantly,nohairpinwasfoundthatknockeddownHOXA9andwhichhadnoeffect
onMMcelllineviability.
DeterminationofDIS3andFAM46Cmutationstatusincelllines
ToidentifysuitablemodelsforfuturefunctionalcharacterizationofDIS3andFAM46Cmutations,we
determinedthemutationstatusinseveralMMcelllines.ForDIS3,weonlyexaminedthecatalyticRNB
domain,inwhichwehadobservedallthemutationsintheprimarypatientsamples.WeperformedPCR
oncDNA(DIS3)orgenomicDNA(FAM46C)withtiledprimerpairs(primersequencesandreaction
conditionsinSupplementaryTable14).WethenperformedSangersequencingusingthesameprimers.
2/15testedcelllineshadpointmutationsintheDIS3RNBdomain(SupplementaryTable15).Both
mutationswereassociatedwithlossoftheotheralleleviachromosome13deletion.4/16testedcell
lineshadmutationsinFAM46C(SupplementaryTable16).Twowerepointmutationsandtwowere
indelsresultinginaframeshift.3/4mutationswereassociatedwithlossoftheotherallelevia1p
deletion.AfifthFAM46Cmutationinanadditionalcellline(LP1)wasidentifiedbyexamining244KaCGH
profilesofMMcelllines(SupplementaryTable16).Thiscomprisedfocalbialleliclossofthe5endof
thegeneandwasassociatedwithabsentFAM46Cexpression(FAM46Cisotherwiseubiquitously
expressedinMM).ThesedatasuggestthattheFAM46Cmutationsresultinlossoffunction.
References
1.
2.
Gnirke,A.,etal.Solutionhybridselectionwithultralongoligonucleotidesformassivelyparallel
targetedsequencing.NatBiotechnol.27,1829(2009).
Ewing,B.,etal.Basecallingofautomatedsequencertracesusingphred.I.Accuracyassessment.
GenomeRes.8,17585(1998).
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20
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numberpolymorphismsandrareCNVs.NatGenet.40,125360(2008).
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Ding,L.,etal.Somaticmutationsaffectkeypathwaysinlungadenocarcinoma.Nature.455,
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Getz,G.,etal.Commenton"Theconsensuscodingsequencesofhumanbreastandcolorectal
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regulatorymodulesinalignedmammaliangenomesequences.GenomeRes.15,105160(2005).
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inBcelllymphoma.ProcNatlAcadSciUSA.92,125204(1995).
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entropyoptimization.GenomeBiol.8,R232(2007).
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doi:10.1038/nature09837
Sample ID
Age at
Diagnosis
Gender
MMRC0004
36
Male
Race
Heavy chain
class
Light chain
class
Caucasian
IgG
Kappa
Hyperdiploidy (HD)
and/or IgH
translocation
Other cytogenetics
Treatment status
Sequencing
method
Untreated
WE
MMRC0028
44
Male
Caucasian
IgG
Not available
t(4;14)
del 13q14
Untreated
WE
MMRC0173
41
Female
Not available
Not available
HD
del 13q14
Treated
WGS
IgG
Lambda
HD
Treated
Both
Cannot assign
Kappa
HD
Untreated
WE
Treated
WGS
Untreated
WE
Treated
WE
Untreated
WE
MMRC0191
56
Female
Asian
African
American
MMRC0216
59
Female
Caucasian
MMRC0242
71
Male
Hispanic
IgG
Lambda
Not available
MMRC0244
56
Female
Caucasian
IgG
Kappa
HD
del 13q14
MMRC0282
60
Male
Caucasian
Not detected
Kappa
HD
MMRC0284
41
Male
Caucasian
Cannot assign
Kappa
t(11;14)
MMRC0286
50
Female
Caucasian
IgA
Kappa
t(14;16)
del 13q14
Untreated
WE
MMRC0308
55
Female
Caucasian
IgG
Lambda
t(4;14)
del 13q14
Treated
WE
del 13q14
Untreated
WGS
MMRC0309
61
Male
Caucasian
IgA
Lambda
t(14;16)
MMRC0319
55
Male
Caucasian
IgM
Kappa
HD; t(4;14)
MMRC0322
69
Male
Caucasian
IgG
Kappa
Not available
del 13q14
Untreated
WGS
del 13q14
Untreated
WE
del 13q14**
MMRC0329
37
Female
Caucasian
IgG
Kappa
HD
Treated
WE
MMRC0332
66
Male
Caucasian
IgG
Lambda
HD; t(4;14)
Treated
WGS
MMRC0335
56
Male
Caucasian
IgA
Kappa
t(11;14)
Treated
WGS
MMRC0338
63
Male
Caucasian
IgG
Kappa
Not available
Untreated
WGS
MMRC0343
62
Male
Caucasian
Not detected
Kappa
t(11;14)
del 13q14; del 17p13
Treated
WGS
Treated
WGS
del 17p13
Untreated
WE
MMRC0344
69
Female
Caucasian
IgG
Lambda
Not available
MMRC0347
58
Male
Caucasian
IgG
Lambda
t(11;14)
MMRC0356
52
Male
Hispanic
IgG
Kappa
HD; t(11;14)*
del 13q14
Untreated
WGS
MMRC0359
63
Male
Caucasian
IgG
Kappa
t(11;14)
del 13q14; del 1p32
Untreated
WE
MMRC0375
72
Male
Caucasian
IgA
Kappa
t(11;14)
del 13q14
Treated
WGS
MMRC0376
56
Male
Caucasian
IgA
Kappa
t(4;14)
del 13q14
Untreated
WGS
MMRC0381
72
Male
Caucasian
IgG
Kappa
HD
del 13q14
Untreated
WE
del 13q14
Treated
WGS
MMRC0383
69
Male
Caucasian
IgG
Kappa
t(11;14)
MMRC0387
60
Female
Caucasian
IgG
Kappa
HD
MMRC0389
37
Male
Caucasian
IgE
Kappa
HD; t(14;20)
MMRC0390
71
Female
Caucasian
IgG
Lambda
t(11;14)
MMRC0392
59
Male
Caucasian
IgG
Lambda
HD; t(6;14)
Untreated
WGS
del 13q14
Treated
WGS
Treated
WGS
del 13q14
Treated
WGS
MMRC0406
59
Female
Caucasian
IgA
Kappa
HD
Untreated
WGS
MMRC0408
58
Male
Caucasian
IgA
Lambda
HD
del 1p32**
Untreated
WGS
MMRC0412
49
Male
Caucasian
IgG
Kappa
HD
del 1p32
Treated
WGS
MMRC0421
45
Male
IgA
Not available
t(4;14)
Treated
WGS
Treated
WE
MMRC0423
51
Male
Caucasian
African
American
IgA
Kappa
MMRC0425
65
Female
Caucasian
IgG
Kappa
Not available
MMRC0427
62
Male
Other
IgG
Lambda
t(11;14)
del 13q14
Untreated
WGS
Treated
WE
*Spiked CCND1 expression absent, despite t(11;14)

** Focal bi-allelic deletion at CDKN2C or RB1
Supplementary Table 1 Clinical characteristics of patients providing samples for

sequencing. Hyperdiploidy and IgH translocations were determined by FISH and/or
aCGH and/or gene expression profiles. Treatment status refers to whether the patient
had received treatment at the time of sample donation.
doi:10.1038/nature09837
Whole Genome (n = 23)
Nonsynonymous point mutations

Missense
Nonsense
Splice site
Read-through
Small indels
Frame-shift deletion
In-frame deletion
Frame-shift insertion
In-frame insertion
Larger rearrangements
Translocations
Deletions
Insertions
Tandem duplications
Long-range
Complex
Whole Exome (n = 16)
Total (n = 39)
Total
Mean
Total
Mean
Total
Mean
721
49
22
1
793
31.3
2.1
1.0
0.04
34.6
416
25
7
0
448
26.1
1.6
0.4
0
28.1
1141
74
29
1
1245
29.3
1.9
0.7
0.03
31.9
5
5
2
1
13
0.2
0.2
0.09
0.04
0.6
4
2
2
0
8
0.3
0.1
0.1
0
0.5
9
7
4
1
21
0.2
0.2
0.1
0.03
0.5
204
105
23
32
78
33
475
8.7
4.6
1.0
1.4
3.4
1.4
20 7
20.7
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
Supplementary Table 2 Somatic events disrupting protein-coding regions. Only

rearrangements with a breakpoint resulting in the disruption of protein coding are
included. Long-range events are those with breakpoints separated by more than 1 Mb.
Complex rearrangements are those involving two or more separate events.
doi:10.1038/nature09837
Gene
A2M
AADAT
AASS
ABCA12
ABCA12
ABCA13
ABCC1
ABCE1
ACAD11
ACAD9
ACBD3
ACBD5
ACOXL
ACTL6A
ACTN3
ACTRT1
ADAD1
ADAM17
ADAM17
ADAM18
ADAM18
ADAM22
ADAM29
ADAM9
ADAMTS1
ADAMTS18
ADAMTS19
ADAMTS2
ADAMTS20
ADAMTS8
ADAMTS9
ADAMTS9
ADAMTSL1
ADAMTSL3
ADCY2
ADCY2
ADNP
ADNP2
AFAP1
AFAP1L1
AFF1
AFG3L2
AGAP2
AGBL4
AHNAK2
AIM1L
AKAP6
AKAP6
AKR1B15
ALCAM
ALCAM
ALDH1A2
ALDH1L1
ALDH1L2
ALMS1
ALOX12B
ALOX12B
ALOX12B
ALOX12B
ALOX15B
ALOX15B
ALOXE3
ALOXE3
ALPK2
AMT
ANGPTL5
ANK2
ANK2
ANK2
Chr
12
4
7
2
2
7
16
4
3
3
1
10
2
3
11
X
4
2
2
8
8
7
4
8
21
16
5
5
12
11
3
3
9
15
5
5
20
18
4
3
4
18
12
1
5
1
14
14
7
3
3
15
3
12
2
17
17
17
17
17
17
17
17
18
3
11
4
4
4
Position
(strand)
9139481
171219720
121528670
215583394
215532039
48362407
16020092(+)
146260624
133858909(+)
130096876
224439435(-)
27537271
111315566(-)
180770623
66086153
127013232
123561875
9562800
9585504
39610001(+)
39644716
87405341(+)
176134318
38984621
27134136
75947338
128960221
178602608(+)
42063959
129781224
64555038
64594464
18896858
82357635
7810576
7837525
48942218
75995981
7827366
143784143(+)
88085017(+)
12341180
56414108
49116754(+)
128274788(+)
26536734
32085771
32084721
133903503
106653896(+)
106606779(-)
56122206(-)
127356171
103983243
73533019
7919747
7920252
7924355
7916890(+)
7884260(-)
7884094(+)
7950718(-)
7951129(+)
54387075(+)
49431460
101276446
114190342
114488891
114494274
2nd gene
Chr
Position
(strand)
PRKCB
16
23931585(-)
NPHP3
133885257(-)
224458761(+)
23
105246739(-)
40122511(-)
93095395(+)
5
4
1
14
3
5
17
SLC37A1
MYH10
PIGL
NTN1
SLC37A1
21
17
17
17
21
18
178711536(-)
148692173(-)
88133105(-)
76244110(-)
104511997(-)
155190940(-)
96552937(-)
50044110(+)
42832836(+)
8412781(-)
16114874(+)
8927833(-)
42833530(-)
54415713(-)
Type
Missense
Splice site
Missense
Missense
Missense
Missense
Long range
Missense
Deletion
Missense
Tandem duplication
Missense
Translocation
Missense
Missense
Missense
Missense
Frame shift deletion
Missense
Deletion
Missense
Long range
Missense
Missense
Missense
Missense
Missense
Deletion
Missense
Nonsense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Deletion
Missense
Missense
Long range
Translocation
Missense
Missense
Nonsense
Nonsense
Long range
Translocation
Translocation
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Inversion
Long range
Inversion
Translocation
Deletion
Missense
Nonsense
Missense
Missense
Missense
AA change
R645H
V379_splice
R466Q
A793D
M1965L
R3435W
N338S
R127K
E403D
D17E
A754T
V212A
F488L
G486fs
D161N
E457K
M356T
R53G
G594A
S487I
N475K
D1514G
Y703*
R1431H
N663T
W1710C
G497R
K657N
S811F
D814N
L565S
G604S
I486V
G506E
P131T
L721I
R371*
Y40*
N212K
E240K
Q1952K
E515D
D500N
L226P
N275K
Q196*
N3K
S1461L
P1684Q
Sample
MMRC0332
MMRC0427
MMRC0392
MMRC0322
MMRC0356
MMRC0191
MMRC0344
MMRC0381
MMRC0191
MMRC0389
MMRC0421
MMRC0389
MMRC0191
MMRC0425
MMRC0412
MMRC0191
MMRC0376
MMRC0427
MMRC0191
MMRC0332
MMRC0338
MMRC0425
MMRC0425
MMRC0347
MMRC0387
MMRC0191
MMRC0332
MMRC0408
MMRC0335
MMRC0191
MMRC0425
MMRC0425
MMRC0332
MMRC0329
MMRC0375
MMRC0412
MMRC0282
MMRC0319
MMRC0387
MMRC0191
MMRC0332
MMRC0309
MMRC0389
MMRC0412
MMRC0191
MMRC0376
MMRC0347
MMRC0406
MMRC0408
MMRC0191
MMRC0375
MMRC0191
MMRC0319
MMRC0344
MMRC0412
MMRC0392
MMRC0392
MMRC0173
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0319
MMRC0392
MMRC0344
MMRC0329
MMRC0389
MMRC0389
Previously
treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Supplementary Table 3 All somatic mutations qualitatively affecting protein

coding. Included are point mutations, small indels, and larger rearrangements with
breakpoints within genes. Complex rearrangements (as detailed in figure 1b) have been
expanded into individual events.
doi:10.1038/nature09837
Gene
ANKRD30A
ANKRD30A
ANKRD50
ANKRD57
ANO3
ANO6
ANTXR2
ANXA13
ANXA2
ANXA2
AP1M1
APOH
AQP7
ARHGAP15
ARHGAP26
ARHGEF10
ARHGEF15
ARHGEF3
ARID1A
ARID2
ARID3C
ARID4A
ARL15
ARMC9
ARNTL2
ARPP-21
ARRDC1
ASB15
ASH1L
ASH1L
ASH2L
ASNS
ASPM
ATAD3A
ATG2A
ATG7
ATM
ATOH1
ATOH8
ATP10B
ATP1A4
ATP2C1
ATP4B
ATP6V0A1
ATP6V1C2
ATP7B
ATP8B4
ATP9A
AUTS2
AXIN2
AXL
AXL
B3GALTL
B4GALNT4
BACE2
BAG4
BAIAP2L1
BAZ2B
BCAN
BCAP29
BCAS4
BCKDHB
BICC1
BLMH
BMP6
BMS1
BRAF
BRCA1
BRE
Chr
10
10
4
2
11
12
4
8
15
15
19
17
9
2
5
8
17
3
1
12
9
14
5
2
12
3
9
7
1
1
8
7
1
1
11
3
11
4
2
5
1
3
13
1
2
8
15
20
7
17
19
19
13
11
17
8
7
2
1
7
20
6
10
17
6
10
7
17
2
Position
(strand)
37548386
37476319
125811674
109730452
26503799
43982136
81016850(+)
124766077
58433523(+)
58431220
16199994
61641168
33375852
142931546(+)
142220883(-)
1830101
8163084
56764144
26967029
44540952
34613427
57842916(+)
53635635(+)
231835342
27412578
35700306
139629369
123057383
153715219
153580068
38091659
97320361
195328870
1445795
64431333
11447811(-)
107629789
94970059
85835519
159982131
158411149
131545181(-)
113351788
224308027(-)
10835279
68849483(-)
47999826
49815595(-)
69233117(+)
60899765(+)
46454269
46454269
30725160(+)
369940
12270501(+)
34928411(-)
97766488(+)
159890491
154886150(+)
107046037
48891729
80937777
60228971
25586084(+)
7615208(-)
42632094
140127871
38510440
28408035(-)
2nd gene
Chr
Position
(strand)
81067994(-)
15
58451240(-)
2
16
KIAA0586
AATK
SALL4
14
14
17
58046228(-)
55603989(-)
76734959(+)
132163563(+)
17
37879120(-)
13
51448093(+)
20
7
17
49839479(-)
69445909(-)
60975400(-)
13
30767593(-)
21
8
15
41533322(-)
38161702(-)
60584713(-)
154902665(+)
17
6
C11orf65
143720455(-)
66403657(+)
11
25605465(-)
7699953(+)
107817836(+)
Supplementary Table 3 (continued)
Type
Missense
Missense
Missense
Missense
Missense
Missense
Deletion
Missense
Deletion
Missense
Missense
Missense
Missense
Deletion
Translocation
Missense
Missense
Frame shift insertion
Missense
Missense
Missense
Deletion
Translocation
Missense
Nonsense
Missense
Missense
Missense
Missense
Nonsense
Missense
Missense
Missense
Missense
Missense
Translocation
Nonsense
Missense
Missense
Missense
Missense
Tandem duplication
Missense
Translocation
Missense
Translocation
Missense
Inversion
Deletion
Deletion
Nonsense
Nonsense
Deletion
Missense
Translocation
Long range
Translocation
Missense
Inversion
Missense
Missense
Missense
Nonsense
Deletion
Tandem duplication
Missense
Missense
Missense
Translocation
AA change
E1191A
S435P
D736E
A366V
G245V
P48L
G262E
N258S
H288P
Q283E
G180R
E466K
R690C
P99fs
D1050E
M1625I
K287M
Y369F
R50*
D86Y
Q420H
E523G
KM1355>NL
R2691*
F254S
T475A
I3077F
A277P
K934N
S646*
L320S
R232S
V554I
G767R
A260T
E315Q
W611S
Y694*
Y694*
R855C
S2043Y
R240T
G125E
D231E
Q560*
V791M
G469A
C44F
Sample
MMRC0242
MMRC0389
MMRC0390
MMRC0359
MMRC0421
MMRC0338
MMRC0191
MMRC0421
MMRC0376
MMRC0421
MMRC0191
MMRC0389
MMRC0375
MMRC0389
MMRC0425
MMRC0387
MMRC0392
MMRC0381
MMRC0356
MMRC0286
MMRC0319
MMRC0319
MMRC0191
MMRC0282
MMRC0028
MMRC0338
MMRC0286
MMRC0242
MMRC0412
MMRC0381
MMRC0329
MMRC0335
MMRC0383
MMRC0375
MMRC0173
MMRC0387
MMRC0191
MMRC0309
MMRC0427
MMRC0335
MMRC0244
MMRC0425
MMRC0406
MMRC0425
MMRC0392
MMRC0319
MMRC0242
MMRC0332
MMRC0332
MMRC0421
MMRC0335
MMRC0343
MMRC0412
MMRC0381
MMRC0392
MMRC0412
MMRC0191
MMRC0332
MMRC0242
MMRC0191
MMRC0329
MMRC0344
MMRC0335
MMRC0191
MMRC0406
MMRC0387
MMRC0344
MMRC0344
MMRC0191
Previously
treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Untreated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
doi:10.1038/nature09837
Gene
BSN
BTBD11
BTBD7
BTLA
BTRC
C10orf111
C10orf118
C10orf72
C10orf84
C10orf96
C11orf24
C11orf61
C11orf90
C12orf11
C12orf11
C12orf30
C12orf35
C13orf30
C14orf43
C15orf55
C16orf91
C17orf46
C17orf68
C17orf68
C17orf71
C18orf19
C19orf33
C1orf101
C1orf14
C1orf14
C1orf163
C1orf26
C1orf64
C1orf95
C20orf107
C20orf117
C20orf117
C20orf132
C20orf152
C20orf194
C20orf20
C20orf26
C22orf43
C2CD3
C2orf61
C2orf71
C2orf71
C2orf86
C2orf86
C3orf38
C3orf64
C4orf43
C5
C5orf34
C6orf125
C6orf138
C6orf146
C6orf15
C6orf170
C7orf50
C9orf30
C9orf78
C9orf85
C9orf93
CA3
CACNA1A
CACNA1B
CACNA1C
CADPS
Chr
3
12
14
3
10
10
10
10
10
10
11
11
11
12
12
12
12
13
1
8
16
17
17
17
17
18
19
1
1
1
1
1
1
1
20
20
20
20
20
20
20
10
22
11
2
2
2
2
2
3
3
4
9
5
6
6
6
6
6
7
9
1
9
9
8
12
9
3
3
Position
(strand)
49664376
106533023
92830943
113667901
103288069
15178691
115881059
49971922(+)
120054455(+)
118101377(+)
67786495
124142701
90014673(-)
12928113(-)
26957771
110994115
32026928
42256206
46481870(-)
57009317(+)
1416310
40693261(-)
8082189(-)
8072916
54642550
13671976
43487387
242790743
181175260
181135742
52926231
183410506
16201730(-)
224830735(+)
54541893
34887558(+)
34899889(-)
35182854
34031821
3199122
60901255
36256547(-)
22294283
73426367
23491513(-)
29148851
29148816
63430182(+)
63430398(-)
88288258
69136988
164647655
122784867
43541813
33786327(+)
48143998
4014219
31187264
121468888
809715(+)
102252848
19228814(-)
73777444
15581381
86541652
10717042(-)
139893325
67360306( )
67360306(-)
62398862
2nd gene
Chr
Position
(strand)
C10orf128
10
10
10
50039012(-))
50039012(
120064906(-)
118197108(-)
PNLIPRP3
11
12
PRPSAP1
MYH10
SAMHD1
SAMHD1
14
15
73270266(+)
32431688(-)
17
17
71851808(+)
8406630(-)
1
22
16203618(-)
21558309(+)
20
20
34974001(-)
34961798(+)
20
23
23
IP6K3
93215404(-)
26956842(-)
19989182(+)
47208515(-)
118279592(+)
118279776(-)
33801238(+)
1015815(-)
131632155(+)
19
13356240(+)
12
2353255( )
2353255(-)
Type
Nonsense
Missense
Missense
Missense
Missense
Missense
Missense
Deletion
Deletion
Deletion
Missense
Missense
Long range
Long range
Missense
Nonsense
Missense
Missense
Translocation
Translocation
Missense
Long range
Inversion
Missense
Missense
Missense
In frame deletion
Missense
Missense
Read-through
Missense
Inversion
Translocation
Missense
Deletion
Tandem duplication
Splice site
Missense
Missense
Missense
Translocation
In frame deletion
Missense
Long range
Missense
Missense
Translocation
Translocation
Missense
Missense
Missense
Missense
Nonsense
Inversion
Missense
Missense
In frame deletion
Missense
Deletion
Nonsense
Translocation
Nonsense
Missense
Translocation
Splice site
Translocation
Missense
AA change
E795*
T652M
R59K
S157T
A536G
S47R
E646D
A182T
G369R
P564L
R335*
A591V
M1I
P105Q
T1081A
S119T
G34A
V88_K89>V
V394F
E274D
*654L
S148fs
V202F
S30N
C659_splice
Q90H
A913P
F144L
D126_A127>A
Q1895H
S594F
D606N
R258L
H170N
K8N
V1093I
W242*
S118F
E413K
G262_G284>G
S1149P
Q203*
E114fs
Q124*
G111R
P95_splice
R1245H
Sample
MMRC0332
MMRC0282
MMRC0322
MMRC0191
MMRC0286
MMRC0282
MMRC0004
MMRC0335
MMRC0191
MMRC0344
MMRC0216
MMRC0412
MMRC0338
MMRC0421
MMRC0421
MMRC0282
MMRC0335
MMRC0347
MMRC0191
MMRC0335
MMRC0392
MMRC0425
MMRC0392
MMRC0322
MMRC0244
MMRC0389
MMRC0412
MMRC0242
MMRC0343
MMRC0383
MMRC0286
MMRC0375
MMRC0406
MMRC0425
MMRC0408
MMRC0387
MMRC0356
MMRC0412
MMRC0359
MMRC0383
MMRC0412
MMRC0191
MMRC0412
MMRC0286
MMRC0191
MMRC0028
MMRC0322
MMRC0335
MMRC0335
MMRC0389
MMRC0406
MMRC0335
MMRC0376
MMRC0392
MMRC0191
MMRC0309
MMRC0389
MMRC0028
MMRC0376
MMRC0392
MMRC0389
MMRC0191
MMRC0356
MMRC0319
MMRC0412
MMRC0344
MMRC0376
MMRC0191
MMRC0332
Previously
treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Untreated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Treated
doi:10.1038/nature09837
Gene
CALCR
CALR3
CAMK1D
CAMK1D
CAMK4
CAMK4
CAMLG
CAMTA1
CAMTA1
CANT1
CAPG
CAPN12
CAPZA1
CARD11
CARD11
CASC1
CASC1
CASC1
CASK
CASP8AP2
CBLB
CBLN1
CCDC111
CCDC123
CCDC123
CCDC144NL
CCDC147
CCDC153
CCDC157
CCDC158
CCDC46
CCDC72
CCL2
CCND1
CCND1
CD109
CD14
CD163
CD1B
CD200
CD244
CD247
CD300LG
CD3G
CDC2
CDC20B
CDC25C
CDC25C
CDC25C
CDC42BPB
CDH11
CDH19
CDH2
CDH2
CDH20
CDH8
CDK4
CDK4
CDK5RAP1
CDON
CDYL
CECR2
CELA1
CELSR2
CENPF
CENPJ
CEP110
CEP170
CEP290
Chr
7
19
10
10
5
5
5
1
1
17
2
19
1
7
7
12
12
12
X
6
3
16
1
19
19
17
10
11
22
4
17
2
17
11
11
6
5
12
1
3
1
1
17
11
10
5
5
5
3
14
16
18
18
18
18
16
12
12
12
11
6
22
12
1
1
13
9
1
12
Position
(strand)
92928104
16454284
12843023
12437494(-)
110842426(+)
110826946(+)
134106601(-)
7727615
7721013
74504779
85482538
43924381
112998752
2930442
2925677
25228630(+)
25229286(-)
25237517(+)
41299822
90615866(+)
106953138
47870979
224073101(+)
38100631(+)
38136359
20710609
106114629
118569089
29096840
77507878
61388149
234756563(-)
29607891
69165273
69165400
74576508
139991746
7545124
156566379
113542439
158691054(-)
165693972(-)
39281478
117728342
62217876
54488620(-)
137689142(-)
137654248
135595261(+)
102522651
63596246
62369362
23836997
23847649
57317640
60412508
56431115
56431697
10328091(-)
125396467
4880867
16351270(-)
50026682
109597054
212882949
24378627
122964045
241395510
87048252
2nd gene
Chr
Position
(strand)
DDX46
X
5
10
5
145395207(-)
111028801(-)
78141709(-)
134141589(+)
PTPRN2
RHPN2
12
12
12
27084669(+)
27064168(+)
27084863(-)
157695832(-)
4
19
SLC30A6
KDM3B
1
2
185850137(+)
38213530(-)
48457441(-)
159071543(+)
32270590(+)
10
5
38545191(-)
137772951(-)
137658217(-)
20
22
31432819(-)
16925642(+)
Type
Missense
Missense
Missense
Translocation
Deletion
Translocation
Tandem duplication
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Long range
Long range
Long range
Missense
Translocation
Nonsense
Missense
Translocation
Deletion
Splice site
Splice site
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Tandem duplication
Translocation
Nonsense
Missense
Missense
Translocation
Inversion
Missense
Translocation
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
Tandem duplication
Missense
Missense
Missense
Missense
Missense
Nonsense
Missense
AA change
V239I
A299P
L124V
W1439S
R1356W
N174I
V26G
F146L
R121T
Y631H
D789N
S606L
W194*
S140L
Q164_splice
A139_splice
I197V
G111S
Q316E
E475K
T589D
P78T
Q4R
K46N
A1146T
T336S
R112H
L165R
V5M
E24*
R166Q
V124G
H208Q
V206L
A10T
V242I
G328S
V132A
P163R
H282Q
G127D
R24L
Q79E
D271N
V3G
T944P
V1549F
W517G
E1727V
S694*
S694
R198K
Sample
MMRC0390
MMRC0308
MMRC0389
MMRC0343
MMRC0332
MMRC0309
MMRC0425
MMRC0242
MMRC0338
MMRC0335
MMRC0347
MMRC0191
MMRC0286
MMRC0375
MMRC0425
MMRC0421
MMRC0421
MMRC0421
MMRC0173
MMRC0191
MMRC0425
MMRC0244
MMRC0344
MMRC0389
MMRC0427
MMRC0242
MMRC0244
MMRC0343
MMRC0347
MMRC0286
MMRC0286
MMRC0191
MMRC0421
MMRC0322
MMRC0335
MMRC0191
MMRC0421
MMRC0387
MMRC0282
MMRC0173
MMRC0356
MMRC0356
MMRC0335
MMRC0383
MMRC0173
MMRC0191
MMRC0344
MMRC0332
MMRC0191
MMRC0390
MMRC0282
MMRC0427
MMRC0383
MMRC0392
MMRC0427
MMRC0387
MMRC0383
MMRC0383
MMRC0344
MMRC0389
MMRC0319
MMRC0425
MMRC0329
MMRC0381
MMRC0322
MMRC0408
MMRC0191
MMRC0332
MMRC0338
Previously
treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
doi:10.1038/nature09837
Gene
CETN2
CFTR
CGN
CGN
CHD3
CHD3
CHD3
CHD9
CHIA
CHIA
CHL1
CHRM2
CHRM3
CHRNA5
CHRNA6
CHRNB2
CHRNB3
CHRND
CHST5
CIR1
CIR1
CKAP5
CKM
CKM
CLCN1
CLIC4
CLIP1
CLIP4
CLMN
CLRN3
CLTC
CLVS2
CMBL
CMKLR1
CMTM2
CMTM7
CMYA5
CMYA5
CNBD1
CNBD1
CNGB3
CNOT6
CNOT6L
CNTN3
CNTN4
CNTN5
CNTNAP2
CNTNAP5
COG5
COL12A1
COL16A1
COL17A1
COL19A1
COL19A1
COL1A1
COL21A1
COL23A1
COL23A1
COL3A1
COL4A3
COL4A6
COL5A2
COL6A6
COL7A1
COL7A1
COPG
COPS3
CORIN
COX11
Chr
X
7
1
1
17
17
17
11
1
1
3
7
1
3
8
1
8
2
16
2
2
11
19
19
7
1
12
2
14
10
17
1
5
12
16
3
5
5
8
8
8
5
4
3
3
11
7
2
7
6
1
10
6
6
17
6
5
5
2
2
X
2
3
3
3
3
2
4
17
Position
(strand)
151748801
117069732
149774199
149757906
7751997
7755593
7749732
74132346(+)
111664495
111656482
379902
136351244
238137889
112366549(+)
42731315
152808899
42605616(+)
233106997
74120718
174923653
174921781
46779415
50507001
50507001
142759173
25039121
121397950
29220129
94739168(-)
129572036
55115537
94566893(+)
10339506
107209782
65171151
32411457(+)
79066681
79065734
83533762(-)
83666013(+)
87710281
179928794
78860752
74497474
3053994
99441414(+)
146814054
124857362(-)
106658328
75856549
31918125(-)
105812026
70694528
70685545(+)
45617947
56143751
177621343
177760406(-)
189580857
227818975
107305075
189673088
131768444
48597513
48603939
130462242
84020364(-)
47361926
50400745
2nd gene
Chr
Position
(strand)
16
51839852(-))
51839852(
15
14
DCTD
8
8
42672519(-)
94949481(+)
123377440(+)
184063778(-)
88093821(-)
88105353(+)
11
99458113(-)
14
46063526(-)
HABP4
76663044(+)
17
31950230(+)
31349810(-)
98284071(+)
17110098(-)
Type
Splice site
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Splice site
Missense
Missense
Tandem duplication
Missense
Missense
Translocation
Missense
Missense
Missense
Translocation
Missense
Missense
Long range
Long range
Missense
Missense
Missense
Missense
Missense
Deletion
Missense
Translocation
Missense
Nonsense
Tandem duplication
Missense
Missense
Translocation
Missense
Missense
Missense
Translocation
Missense
Missense
Missense
Nonsense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
AA change
K54_splice
G1241V
L988V
S96L
G1755V
P2049S
V1462I
P331T
T68I
Q474L
K364N
R172K
R96H
R73Q
A387V
R356C
Q220K
S348N
T332A
G167C
G167C
I987T
K199_splice
I466M
M233I
S108Y
R1350T
M142I
T363I
E47V
I2113V
P1797Q
D488N
S369Y
P509T
C339F
R364W
T589P
L743F
R2980*
G297D
I91M
L1437P
V259I
P230A
G1122D
K129T
G953R
L120*
Q497H
R1312H
G533V
A344T
E490G
R88W
Sample
MMRC0344
MMRC0191
MMRC0329
MMRC0389
MMRC0329
MMRC0338
MMRC0412
MMRC0343
MMRC0335
MMRC0392
MMRC0376
MMRC0412
MMRC0387
MMRC0344
MMRC0408
MMRC0387
MMRC0392
MMRC0421
MMRC0347
MMRC0381
MMRC0383
MMRC0421
MMRC0319
MMRC0173
MMRC0308
MMRC0282
MMRC0329
MMRC0343
MMRC0425
MMRC0332
MMRC0375
MMRC0332
MMRC0387
MMRC0343
MMRC0282
MMRC0309
MMRC0375
MMRC0389
MMRC0421
MMRC0421
MMRC0335
MMRC0338
MMRC0421
MMRC0332
MMRC0173
MMRC0319
MMRC0004
MMRC0191
MMRC0389
MMRC0423
MMRC0421
MMRC0425
MMRC0375
MMRC0309
MMRC0216
MMRC0392
MMRC0375
MMRC0309
MMRC0338
MMRC0389
MMRC0335
MMRC0191
MMRC0412
MMRC0356
MMRC0427
MMRC0412
MMRC0332
MMRC0427
MMRC0356
Previously
treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
doi:10.1038/nature09837
Gene
CPEB4
CPSF3
CPXM2
CRB1
CREBBP
CRHBP
CRIPAK
CRYBG3
CSDE1
CSMD2
CSMD2
CSMD3
CSNK1G3
CSPG4
CSRNP3
CTCFL
CTNNA3
CTNNA3
CTNNAL1
CTNND1
CTNND2
CTTN
CUBN
CUEDC2
CUL5
CUL7
CUX2
CUX2
CXorf22
CXorf57
CYC1
CYLD
CYP11B2
CYP2F1
CYP8B1
DAPK1
DAPK1
DAPK1
DAPK1
DAPK1
DCAF12L1
DCC
DCC
DCHS1
DCHS2
DCHS2
DCHS2
DCLK2
DCT
DDX11
DDX11
DDX23
DDX25
DENND1B
DENND4C
DENND4C
DHDDS
DHRS11
DHX15
DIAPH2
DIAPH2
DIS3
DIS3
DIS3
DIS3
DISP2
DKFZp761E198
DKK2
DLG2
Chr
5
2
10
1
16
5
4
3
1
1
1
8
5
15
2
20
10
10
9
11
5
11
10
10
11
6
12
12
X
23
8
16
8
19
3
9
9
9
9
9
X
6
18
11
4
4
4
4
13
12
12
12
11
1
9
1
1
17
4
X
X
13
13
13
13
15
11
4
11
Position
(strand)
173309189
9517178
125584026(-)
195657415
3730528(-)
76287446
1379363
99048698(+)
61119464(-)
33962836
33931142
114100564
122954080
73769113
166244255
55517213
67991751(+)
68878041(-)
110794886
54736581(+)
11399603
69940833
17125964
104173261
107418816(+)
43124247
110213632
110256876
35854181
105784286(-)
145223274
49378431(+)
143996171
46319298
42891855
89507784
89511987
89486233
89409460(+)
89409470(-)
125512984
127201041(-)
48866177(+)
6601555
155438464
155377120
155377152
151373029
93912536(+)
31129245
31133348
47520116
125292218
196003820(-)
19336503
201999182(-)
26652949(+)
32022689
24159734
96197114(+)
96053996
72244372
72234065
72244028
72234108
38443358
65303756
108175987
82850778
2nd gene
Chr
Position
(strand)
10
126067313(+)
16
20164701(+)
3
1
HPSE2
10
10
100583403(-)
69072547(+)
11
57328220(-)
11
FAM70B
FAM70B
99088815(-))
99088815(
115075967(+)
128642410(+)
23
125251872(-)
16
49379310(-)
13
13
113629070(-)
113629456(+)
18
X
48821684(+)
101299697(-)
13
94254023(-)
DENND1A
125217126(+)
FHOD3
9
18
19318941(+)
32169734(-)
96276850(-)
Type
Missense
Missense
Tandem duplication
Missense
Long range
Splice site
Missense
Deletion
Long range
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Long range
Tandem duplication
Missense
Long range
Nonsense
Missense
Missense
Missense
Long range
Nonsense
Missense
Missense
Missense
Long range
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Translocation
Missense
Translocation
Translocation
Nonsense
Missense
Missense
Missense
Missense
Deletion
Missense
Missense
Missense
Missense
Translocation
Missense
Translocation
Translocation
Missense
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
AA change
S510F
S589L
F612L
P182_splice
T355I
R878C
E1303K
P273L
L307I
R450W
V502I
G510V
N122K
Y503*
G175A
S1233P
R259Q
Q706*
R110H
V1059I
K126Q
R167Q
R30W
R194C
T153M
H964Q
K1394R
G699E
A430E
S2643
S2643*
N1696S
H2257N
I2246T
E463K
R186W
R263Q
D121N
I300M
V961I
G46D
E364K
F201V
S447R
R750K
V474G
G736R
H120Q
E205K
N71D
M807I
Sample
MMRC0338
MMRC0390
MMRC0425
MMRC0335
MMRC0421
MMRC0387
MMRC0284
MMRC0392
MMRC0408
MMRC0335
MMRC0347
MMRC0308
MMRC0390
MMRC0309
MMRC0392
MMRC0309
MMRC0332
MMRC0319
MMRC0322
MMRC0421
MMRC0347
MMRC0309
MMRC0322
MMRC0375
MMRC0375
MMRC0322
MMRC0004
MMRC0216
MMRC0284
MMRC0392
MMRC0308
MMRC0335
MMRC0286
MMRC0383
MMRC0381
MMRC0282
MMRC0308
MMRC0335
MMRC0425
MMRC0425
MMRC0383
MMRC0338
MMRC0387
MMRC0389
MMRC0389
MMRC0392
MMRC0173
MMRC0322
MMRC0356
MMRC0329
MMRC0375
MMRC0329
MMRC0389
MMRC0332
MMRC0421
MMRC0383
MMRC0191
MMRC0282
MMRC0389
MMRC0356
MMRC0406
MMRC0308
MMRC0319
MMRC0343
MMRC0421
MMRC0389
MMRC0389
MMRC0332
MMRC0286
Previously
treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Untreated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
doi:10.1038/nature09837
Gene
DMXL1
DMXL2
DMXL2
DNAH11
DNAH5
DNAH5
DNAH9
DNAH9
DNAH9
DNAJA1
DNAJC14
DNM2
DNMT3B
DNMT3B
DOCK10
DOCK3
DOCK4
DOCK8
DOLK
DONSON
DOPEY2
DOT1L
DPP6
DPY19L2
DRD2
DRD3
DSCAM
DSCAM
DSCAM
DSG1
DSPP
DST
DST
DST
DSTYK
DYSF
EED
EFCAB3
EFHC1
EFNA4
EGFR
EGLN3
EGR1
EHBP1
EHMT1
EIF3B
ELAVL2
ELF2
ELOVL3
EMID1
ENOX1
EP400
EPB41L3
EPHA5
EPHA6
EPHA6
EPHA7
EPHA7
EPHB1
EPHB3
EPHB3
EPHB4
EPYC
ERBB2IP
ERBB2IP
ERBB3
ERC1
ERLIN1
Chr
5
15
3
7
5
5
17
17
17
9
12
19
20
20
2
3
7
9
9
21
21
19
7
12
4
3
21
17
17
18
4
6
6
6
1
2
11
17
6
1
7
14
5
2
9
7
9
4
10
22
13
12
18
4
3
3
6
6
3
3
3
7
12
5
5
12
12
10
Position
(strand)
118513835
49550868
39389102(+)
21688701(+)
13967660
13897959
11548440
11543776
11538956(-)
33020498
54508123
10795538
30848280
30832882
225389675
50941199(-)
111330149(-)
366301
130748152
33878793
36587690
2167622
153794042(+)
62343861
52583111(-)
115341045
40472889
11861613(+)
14820911(-)
27180053
88756533
56491665(+)
56577270
56505221
96264245(-)
71642546
85660516(+)
57847388
52425580
153308070
55236444
33465977
137829376
63077366
139827373
2385341
23694928
140200998
103976305
27940941
42798568
131095428
5396904
66098050(+)
98850840(+)
98925845(-)
94025844
94185719
136273401(+)
185777638
185773037
100241140
89920434
65385594
65355987
54760558(+)
1215386(+)
101927910
2nd gene
FAM3B
Chr
Position
(strand)
15
19
49670533(+)
37979626(+)
21
19
7
95567529(+)
11
112796764(+)
SRRM4
40946326(+)
40934450(-)
56692575(-)
203401185(-)
11
85675554(-)
4
3
12
WNT5B
54424331(+)
115106315(+)
21
21
ARHGAP24
41624442(+)
12
12
86845602(-)
99018634(-)
117926083(+)
136342717(-)
54941789(-)
1619954(-)
Type
Missense
Missense
Translocation
Translocation
Missense
Missense
Missense
Nonsense
Translocation
Missense
Missense
Missense
Missense
Splice site
Splice site
Translocation
Long range
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Translocation
Missense
Missense
Translocation
Translocation
Missense
Missense
Deletion
Missense
Missense
Long range
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Long range
Deletion
Translocation
Missense
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Missense
Deletion
Deletion
Missense
AA change
D1472N
D2411E
E430G
K1753T
D1783N
Q1626*
Q1626
Q159P
R196K
S615L
K421E
Q68_splice
T1090_splice
T734S
P418A
T253N
Q2283P
G756S
R132C
P239T
S928P
M665K
N1232S
E2835G
I3544S
E804D
R428K
T237P
R196H
D1006Y
V210L
Q9H
A1093T
A988T
Y760F
D159N
S303P
A4T
R43L
R377Q
K2253R
T741S
A625T
F21Y
A443T
Q79K
R866H
F14I
T898A
D257A
E92K
Sample
MMRC0191
MMRC0173
MMRC0343
MMRC0376
MMRC0322
MMRC0335
MMRC0322
MMRC0389
MMRC0392
MMRC0319
MMRC0028
MMRC0387
MMRC0191
MMRC0173
MMRC0335
MMRC0383
MMRC0191
MMRC0356
MMRC0329
MMRC0375
MMRC0309
MMRC0381
MMRC0173
MMRC0191
MMRC0392
MMRC0338
MMRC0308
MMRC0392
MMRC0392
MMRC0383
MMRC0332
MMRC0375
MMRC0390
MMRC0412
MMRC0191
MMRC0335
MMRC0421
MMRC0191
MMRC0216
MMRC0376
MMRC0390
MMRC0244
MMRC0282
MMRC0381
MMRC0423
MMRC0343
MMRC0383
MMRC0244
MMRC0390
MMRC0347
MMRC0389
MMRC0191
MMRC0284
MMRC0344
MMRC0319
MMRC0389
MMRC0359
MMRC0389
MMRC0356
MMRC0191
MMRC0282
MMRC0347
MMRC0335
MMRC0319
MMRC0421
MMRC0412
MMRC0191
MMRC0389
Previously
treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
doi:10.1038/nature09837
Gene
ESR1
ESYT1
ETNK1
EVI5
EWSR1
EWSR1
EXOC6
EXOSC2
EYA4
EYS
F3
F5
FA2H
FAF1
FAF2
FAM115A
FAM116A
FAM120A
FAM120B
FAM12A
FAM134B
FAM135A
FAM135B
FAM153B
FAM155A
FAM155A
FAM174A
FAM174A
FAM18B2
FAM190A
FAM190A
FAM190A
FAM190B
FAM38B
FAM46C
FAM46C
FAM46C
FAM46C
FAM46C
FAM47B
FAM5B
FAM5C
FAM73B
FAM82A2
FAM83H
FANCB
FAT3
FAT3
FAT3
FAT3
FBN3
FBXL13
FBXL19
FBXW12
FBXW12
FCGBP
FCHSD2
FCRL2
FEN1
FFAR2
FGA
FGA
FGF6
FGFR2
FGG
FGGY
FHDC1
FHDC1
FIG4
Chr
6
12
12
1
22
22
10
9
6
6
1
1
16
1
5
7
3
9
6
14
5
6
8
5
13
2
5
5
17
4
4
4
10
18
1
1
1
1
1
23
1
1
9
12
8
X
11
11
11
11
19
7
16
3
3
19
11
1
11
19
4
4
12
10
4
1
4
4
6
Position
(strand)
152457336
54813701
22703262
92936075
27915334(+)
28000740(+)
94633807(+)
132568055(-))
132568055(
133875588
66261477
94774262
167772526
73305596
50742413(+)
175842798(-)
143204463
57594099
95358144(-)
170469940
20285657
16538412(-)
71243741
139233957
175461190
107316728
58643357(+)
99925862(+)
99925884(-)
15389837
91312895(+)
91741790(+)
91838617(+)
86175545
10670234
117967150
117967569
117967621
117967557
117967954
34871321(+)
175493103
188458384(+)
130845216(+)
14767152(-)
144880320
14793391
90023454(+)
91727410
91726190
91726313
8102579
102359616
30860980
48389575(+)
48391853
45060581
72342786(-)
156005059
61320050
40632784
155726959
155726404
4413697
123253372
155753196
59797002(+)
154083946
154117155
110219423
2nd gene
C1orf185
NALCN
AUTS2
PPP2R4
Chr
Position
(strand)
22
22
10
9
28014414(-)
28048145(-)
94748129(-)
132569509(-))
132569509(
1
23
13
68960111(+)
106644312(-)
92957371(-)
92957369(+)
4
4
4
91455046(-)
92050647(-)
91993399(-)
23
34958336(-)
1
9
15
188673956(-)
130929149(-)
38832870(-)
FAM159B
100726293(+)
13
14
14
11
ARHGEF17
51358905(-)
93410042(-)
11
92182626(-)
48390034(-)
72707119(+)
64028255(+)
Type
Missense
Missense
Missense
Missense
Deletion
Deletion
Deletion
Inversion
Missense
Missense
Missense
Missense
Missense
Deletion
Translocation
Missense
Missense
Translocation
Missense
Missense
Translocation
Missense
Missense
Missense
Missense
Translocation
Translocation
Translocation
Missense
Deletion
Deletion
Deletion
Missense
Missense
In frame deletion
Missense
Missense
Missense
Deletion
Missense
Deletion
Deletion
Translocation
Missense
Missense
Long range
Missense
Missense
Missense
Missense
Missense
Missense
Deletion
Missense
Missense
Tandem duplication
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Nonsense
Missense
AA change
Q498P
L452F
N244S
L276P
D417N
C183F
T87S
D1605N
T371M
R58C
S429F
D513N
N26K
H176P
L648P
L222F
Q73R
T150R
P595L
N2525K
I46fs
I186del
S203C
D182Y
V314G
R210Q
G1100E
K55Q
S828R
I422F
E463K
R617C
S242N
RR468>RW
E98Q
V4203M
E218K
Q214R
G110R
G358R
E543K
R191Q
T366M
H6Y
R96Q
R1088
R1088*
P778S
Sample
MMRC0329
MMRC0359
MMRC0338
MMRC0356
MMRC0343
MMRC0343
MMRC0387
MMRC0338
MMRC0425
MMRC0381
MMRC0191
MMRC0389
MMRC0173
MMRC0408
MMRC0191
MMRC0329
MMRC0286
MMRC0191
MMRC0309
MMRC0375
MMRC0191
MMRC0309
MMRC0173
MMRC0406
MMRC0381
MMRC0387
MMRC0425
MMRC0425
MMRC0412
MMRC0319
MMRC0421
MMRC0319
MMRC0390
MMRC0335
MMRC0412
MMRC0406
MMRC0216
MMRC0390
MMRC0408
MMRC0319
MMRC0332
MMRC0421
MMRC0191
MMRC0335
MMRC0308
MMRC0387
MMRC0338
MMRC0191
MMRC0376
MMRC0389
MMRC0381
MMRC0329
MMRC0335
MMRC0406
MMRC0309
MMRC0381
MMRC0356
MMRC0389
MMRC0282
MMRC0308
MMRC0356
MMRC0389
MMRC0173
MMRC0356
MMRC0376
MMRC0319
MMRC0423
MMRC0383
MMRC0286
Previously
treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Untreated
Untreated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
doi:10.1038/nature09837
Gene
FKBP5
FLG
FLG2
FLJ20184
FLJ43860
FLNC
FLRT2
FMN1
FMN1
FMO1
FNBP1
FNDC3A
FNDC3A
FNTB
FOXK1
FOXO3
FOXP1
FOXP2
FRK
FRMD3
FRMPD1
FRYL
FSCB
FXYD6
G6PC2
GAA
GAB2
GAB2
GABRA1
GABRB1
GABRB2
GABRB3
GABRG1
GABRG1
GABRR3
GAL3ST3
GALNT9
GALNTL4
GAS2L3
GCET2
GCET2
GHR
GIT1
GJB4
GJD2
GLB1L2
GLIPR1L2
GLP2R
GLRA1
GLT6D1
GMCL1
GNAL
GNB3
GNMT
GNPAT
GP2
GPATCH2
GPATCH2
GPATCH8
GPATCH8
GPC6
GPC6
GPC6
GPD1
GPI
GPR109A
GPR109B
GPR112
GPR115
Chr
6
1
1
4
8
7
14
15
13
1
9
13
13
14
7
6
3
7
6
9
9
4
14
11
2
17
11
11
5
3
5
15
4
4
3
11
12
11
12
3
3
5
17
1
15
11
12
17
5
9
2
6
12
6
1
16
1
1
17
17
13
13
13
12
19
12
12
X
6
Position
(strand)
35651654
150543421
150592174
106028973(+)
138372705(+)
128271111
85157648
31048687
87772249(-)
169511175
131710989
48485221(+)
48497043(+)
64580830
4763284
109021861(-)
71109797
113998137
116370951
85230753(-)
37727115
48303252
44043760
117218642
169466275
75696270
77761957(-)
77609971(+)
161232700
142881392(-)
160819394
24344125
45762306
45761281
99213914
65567324
131319962(+)
11271295
99540293
17806021(-)
113325271
33269949(+)
24928298
35000047
32832230
133744914
74103057
9677917
151208817(-)
137656168
69930294
85388419(-)
6825177
43038011
229468482
20242741(-)
215860109
215733075(+)
39848388(+)
39863458(+)
60893557(-)
61358472(-)
61381281(-)
48785727
39576490
121753516
121766287
135256213
47783927
2nd gene
Chr
Position
(strand)
4
8
106757763(-)
142514381(-)
15
13
13
17
LIMK2
NARS2
CSNK1E
22
48556445(-)
48638419(-)
40800755(+)
29971364(-)
11
22
77868861(+)
37022655(-)
46802698(-)
17
67973231(+)
113325891(-)
42718868(-)
18
PRKCB
31142435(-)
10438247(+)
11704387(-)
16
23931582(+)
2
17
17
13
13
13
190451622(-)
39891813(-)
39902861(-)
93655919(-)
92972239(-)
93099690(+)
Type
Missense
Missense
Missense
Deletion
Long range
Missense
Missense
Missense
Translocation
Missense
Splice site
Deletion
Deletion
Missense
Missense
Translocation
Missense
Missense
Missense
Translocation
Missense
Missense
Missense
Splice site
Missense
Missense
Tandem duplication
Translocation
Splice site
Translocation
Nonsense
Missense
Missense
Missense
Missense
Missense
Translocation
Nonsense
Splice site
Long range
Nonsense
Long range
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
Translocation
Missense
Missense
Missense
Long range
Missense
Translocation
Deletion
Deletion
Long range
Long range
Long range
Missense
Missense
Missense
Missense
Missense
Missense
AA change
V437G
G3522D
R1571K
Y946F
A13S
S613Y
M130L
R432_splice
R291C
R395Q
P407L
S100T
S411C
S475F
Y234S
E727D
A20_splice
I63T
L312R
E86_splice
W91*
D444N
K125T
E187K
R165H
P176A
Q512*
R252_splice
Y86*
S368G
L202R
C236Y
D345N
M231L
D86E
W143G
F284V
Y289S
K97R
T291I
G138W
S117A
Q295K
R90C
I317M
S894R
D34E
Sample
MMRC0406
MMRC0389
MMRC0028
MMRC0332
MMRC0421
MMRC0191
MMRC0309
MMRC0389
MMRC0191
MMRC0332
MMRC0421
MMRC0375
MMRC0375
MMRC0338
MMRC0322
MMRC0356
MMRC0004
MMRC0423
MMRC0359
MMRC0387
MMRC0322
MMRC0427
MMRC0322
MMRC0356
MMRC0286
MMRC0028
MMRC0356
MMRC0191
MMRC0329
MMRC0191
MMRC0390
MMRC0412
MMRC0322
MMRC0389
MMRC0356
MMRC0329
MMRC0242
MMRC0329
MMRC0406
MMRC0343
MMRC0408
MMRC0335
MMRC0389
MMRC0308
MMRC0329
MMRC0344
MMRC0284
MMRC0173
MMRC0387
MMRC0359
MMRC0284
MMRC0389
MMRC0383
MMRC0308
MMRC0028
MMRC0344
MMRC0359
MMRC0343
MMRC0421
MMRC0332
MMRC0392
MMRC0392
MMRC0392
MMRC0173
MMRC0286
MMRC0356
MMRC0004
MMRC0173
MMRC0173
Previously
treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Treated
Untreated
Untreated
Untreated
Treated
Untreated
Untreated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
doi:10.1038/nature09837
Gene
GPR143
GPR155
GPR158
GPR83
GPR98
GPR98
GPRC6A
GPRIN2
GRB2
GRIA2
GRIA4
GRID1
GRID1
GRID1
GRID1
GRIK1
GRIK2
GRIP1
GRM7
GRM7
GRM8
GSTO2
GTF2F2
GTF3C1
GUCY1A2
H2AFY2
HAO1
HAS2
HCFC2
HCLS1
HCN1
HCN1
HCN2
HDAC9
HEATR5A
HECW1
HECW1
HEPHL1
HES3
HEXB
HHIPL2
HIPK1
HIST1H2AC
HIST1H3A
HIST1H4D
HIVEP1
HIVEP3
HKDC1
HLA-A
HLA-A
HMGCL
HMGCR
HMGCS2
HNF4A
HNMT
HNRNPUL2
HOXD13
HPD
HPSE2
HRH4
HS2ST1
HS3ST4
HS3ST4
HS6ST3
HSD17B1
HSP90AB1
HSPA4
Chr
X
2
10
11
5
5
6
10
4
4
11
10
10
10
8
21
6
12
3
3
7
10
13
16
11
10
20
8
12
3
5
5
3
7
8
7
7
11
1
5
1
1
6
6
6
6
1
10
6
6
1
5
1
20
2
11
2
12
5
18
1
16
16
13
17
6
5
Position
(strand)
9667654
174551041(+)
25901622
93753016
90021565
90086696
117220698
46420033
89357014(-)
158462134
104659366(+)
87363311
87618868
87369647
49728873(-)
29849375
101469309(+)
65221917
7163215
7588164(+)
126197269
106029219
44701741(+)
19002992(+)
106354736(-)
71523528
7814483
122698594
103016264
122834005
19981971(+)
27587136(-)
197328869(-)
18820223(+)
13898318(+)
43318040
43450980
93458977
6227248
74020966
220782114
114310366
26232749
26128983
26297180
12248762(+)
41818588
70675849
30018667
30018672
24016623
74682861
120108530
42486171
138484576(+)
62247643
176667595
120779655
40850563(+)
20310982
87330920
17023278(-)
24294544(+)
96283082
37959117
44328839
132431102
2nd gene
C18orf34
SIAH3
Chr
Position
(strand)
175014250(-)
17
70835809(+)
11
105191433(-)
10
87939728(-)
102332800(-)
18
13
16
11
5
5
19
7
14
23
10
16
16
28973325(+)
45285735(+)
27392966(+)
130034355(+)
45628215(-)
45627949(+)
563639(+)
19816336(-)
30859784(-)
83151704(-)
138623739(-)
100720127(-)
25797138(-)
25813970(+)
Type
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Nonsense
Translocation
Missense
Deletion
Missense
Missense
Missense
Translocation
Missense
Deletion
Missense
Missense
Translocation
Missense
Missense
Inversion
Long range
Long range
Missense
Missense
Missense
Nonsense
In frame insertion
Long range
Long range
Translocation
Deletion
Translocation
Missense
Missense
Missense
Nonsense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Deletion
Missense
Missense
Missense
Translocation
Missense
Nonsense
Long range
Long range
Missense
Missense
Missense
Missense
AA change
S331T
I518T
Q407E
E2208K
E3840K
L694S
R383*
R383
K225T
D812Y
R277M
A773S
E826Q
D73N
V199A
A415T
E156D
T170S
A281V
S221T
S585*
P368>PEPEP
V61F
R562C
T685K
Y45*
Q119H
I327M
T403I
A104S
A96V
I35T
G1490S
K295M
I76M
Q78R
D61G
V385A
R116H
R331H
E295K
R308H
S54T
Q123K
R190*
A349P
G134S
R604Q
L87R
Sample
MMRC0173
MMRC0332
MMRC0028
MMRC0332
MMRC0191
MMRC0412
MMRC0343
MMRC0308
MMRC0191
MMRC0282
MMRC0338
MMRC0284
MMRC0383
MMRC0390
MMRC0191
MMRC0286
MMRC0421
MMRC0286
MMRC0242
MMRC0309
MMRC0389
MMRC0309
MMRC0392
MMRC0344
MMRC0338
MMRC0028
MMRC0322
MMRC0343
MMRC0389
MMRC0173
MMRC0344
MMRC0344
MMRC0343
MMRC0392
MMRC0191
MMRC0282
MMRC0389
MMRC0335
MMRC0335
MMRC0191
MMRC0216
MMRC0344
MMRC0282
MMRC0425
MMRC0173
MMRC0335
MMRC0408
MMRC0335
MMRC0427
MMRC0427
MMRC0191
MMRC0427
MMRC0387
MMRC0329
MMRC0421
MMRC0389
MMRC0308
MMRC0322
MMRC0191
MMRC0004
MMRC0322
MMRC0344
MMRC0344
MMRC0389
MMRC0389
MMRC0390
MMRC0338
Previously
treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
doi:10.1038/nature09837
Gene
HSPA8
HTR1A
HTR3D
IARS
IBTK
IDE
IDE
IDH3A
IFFO2
IFI44
IFNAR2
IFT122
IGF1R
IGF2BP1
IGSF3
IGSF3
IGSF5
IHH
IKBIP
IKBKB
IL10RA
IL1RL2
IL24
IL4R
IL6ST
ILDR2
IMMP2L
IMP5
INO80
INO80D
INSR
INTS12
INTS4
IPMK
IPMK
IPPK
IRF4
IRF4
IRF8
IRGC
IRX5
ISPD
ISPD
ITFG1
ITGA10
ITGAE
ITGB1
ITGB1BP3
ITGB6
ITGB6
ITIH5L
ITIH5L
IVNS1ABP
JAG2
JAK2
JAKMIP3
JAM3
JMJD4
JUND
KCNA4
KCNC1
KCNH1
KCNH4
KCNH5
KCNH7
KCNJ12
KCNT2
KCTD1
KCTD17
Chr
11
5
3
9
6
10
10
15
1
1
21
3
15
17
1
1
21
2
12
8
11
2
1
16
5
1
7
17
15
2
19
4
11
10
10
9
6
6
16
19
16
7
7
16
1
17
6
19
2
1
X
X
1
14
9
10
11
1
19
11
11
1
17
14
2
17
1
18
22
Position
(strand)
122377330(+)
63292924
185239345
94031231
83006718
94292538(+)
94284405
76248382
19136695(-)
78898899
33541667(+)
130721131
97283159
44470556
116923808
116923808
40059472
219628513
97531523
42283051
117375238
102171968
205142030
27204079(+)
55280693(-)
165161836(+)
110426992(-)
41278774
39153881
206615660(-)
7123394
106823393
77272573
57784079(+)
57784853(-)
94451674
339972
339972
84504299
48915458
53522742
16284326
16412368
46020294
144239081
3611959
129195685(-)
3890920
160702875
99682944(-)
54798187
54794283
183536017
104683150
5067542
133816510
91489467(+)
225986811
18252535
29990511
17750190
209364145(+)
37583717
62244770
163401353
21259375
194562479
22293888
35785309
2nd gene
Chr
11
10
ST3GAL3
USH2A
Position
(strand)
122436746(-)
94301591(-)
44136921(+)
21
33543218(+)
16
5
1
7
11
10
10
10
11
27270827(-)
55295034(+)
213992413(-)
114862969(-)
43948564(-)
59628825(+)
59628838(-)
33244408(+)
160751148(-)
133499676(+)
209364915(-)
Type
Deletion
Missense
Missense
Splice site
Missense
Deletion
Missense
Nonsense
Long range
Missense
Inversion
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Deletion
Tandem duplication
Long range
Long range
Missense
Missense
Translocation
Missense
Missense
Missense
Long range
Long range
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Nonsense
Missense
Translocation
Missense
Missense
Translocation
Missense
Missense
Missense
Missense
Missense
Missense
Long range
Missense
Missense
Nonsense
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Splice site
Missense
AA change
L127V
S418L
G1095_splice
D69N
H134P
R361
R361*
I362T
V1109L
V821I
Q143H
D1021E
D1021E
V81I
Q299R
E342K
K171E
T470R
D20G
A176E
K241M
N436Y
S392L
M445I
R889L
S99F
K123R
K123R
R170Q
R303H
A44V
K296Q
R126H
P193S
W55*
L105W
R116C
G397S
G1064W
P1203R
D442N
R934H
E652K
A687V
D433N
E254K
Y97*
T325A
R171L
Q726E
A83S
R43H
L756S
D104 splice
D104_splice
I173T
Sample
MMRC0191
MMRC0308
MMRC0308
MMRC0191
MMRC0421
MMRC0389
MMRC0343
MMRC0383
MMRC0191
MMRC0319
MMRC0338
MMRC0389
MMRC0308
MMRC0284
MMRC0216
MMRC0322
MMRC0028
MMRC0329
MMRC0319
MMRC0427
MMRC0309
MMRC0390
MMRC0335
MMRC0392
MMRC0191
MMRC0191
MMRC0191
MMRC0322
MMRC0242
MMRC0191
MMRC0308
MMRC0389
MMRC0343
MMRC0425
MMRC0425
MMRC0392
MMRC0390
MMRC0423
MMRC0322
MMRC0347
MMRC0028
MMRC0332
MMRC0387
MMRC0406
MMRC0389
MMRC0389
MMRC0319
MMRC0322
MMRC0406
MMRC0242
MMRC0319
MMRC0173
MMRC0344
MMRC0242
MMRC0242
MMRC0383
MMRC0338
MMRC0191
MMRC0308
MMRC0309
MMRC0028
MMRC0408
MMRC0335
MMRC0389
MMRC0338
MMRC0335
MMRC0322
MMRC0406
MMRC0356
Previously
treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Untreated
doi:10.1038/nature09837
Gene
KCTD19
KCTD7
KDM3B
KDM3B
KDM3B
KDM6A
KHDRBS3
KIAA0100
KIAA0125
KIAA0182
KIAA0319
KIAA0319L
KIAA0391
KIAA0556
KIAA0802
KIAA0922
KIAA1009
KIAA1009
KIAA1024
KIAA1109
KIAA1244
KIAA1279
KIAA1409
KIAA1467
KIAA1468
KIAA1486
KIAA1614
KIAA1755
KIAA1755
KIF1A
KIF3C
KIF6
KIFC1
KIR2DS4
KIRREL3
KLHL6
KLK15
KLK9
KLRC2
KRAS
KRAS
KRAS
KRAS
KRAS
KRAS
KRAS
KRAS
KRAS
KRAS
KRBA2
KRBA2
KRT31
KSR2
LAMA2
LAMA4
LAMA4
LAMA5
LAMB1
LAMB2
LAMC3
LARS2
LASS3
LCE3A
LGALS3
LGR5
LILRA2
LINGO2
LINGO4
LIPC
Chr
16
7
5
5
5
X
8
17
14
16
6
1
14
12
18
4
6
6
15
4
2
10
14
12
18
2
1
20
13
2
2
6
6
19
11
3
19
19
12
12
12
12
12
12
12
12
12
12
12
17
17
17
12
6
6
6
20
7
3
9
3
15
1
14
12
19
9
1
15
Position
(strand)
65885137
65735278(-)
137765194(+)
137767569(-)
137769281(+)
44834083
136493662(+)
23990586
105400359(+)
84262123
24659718
35682448
34662805
91590012(+)
8815103
154614335(+)
84909851(+)
84895756(-)
77535890
123488211
64689541(+)
70430283
93153362
13102703
58093609
226155904
179162140(+)
36285373
60129309(-)
241314929
26032731
39433094
33479716
60042774
126043158(+)
184755845
56022207
56198824
10479798
25271542
25269829
25271535
25289529
25269829
25269914
25271542
25271538
25289548
25269829
8210763(-)
8214118
36805031
116519582(+)
129241534(+)
112635034
112619741
60345216
107414014
49135612
132904156
45417370(-)
98837769
150862174
54674555
70123383(-)
59778650
27939072
150041224
56640364
2nd gene
ADK
Chr
Position
(strand)
23
8
8
8
20321462(-)
42489268(+)
42487492(-)
42487795(+)
136597182(-)
14
105453725(-)
16
27528637(-)
8
6
10
28506098(+)
85035429(+)
75782773(-)
138624939(+)
179174736(-)
20
36297694(+)
11
17
17
6
12
19
126701882(-)
8214067(-)
67520926(-)
129397206(-)
99765359(+)
47133190(+)
Type
Missense
Translocation
Translocation
Translocation
Translocation
Missense
Deletion
Missense
Deletion
Missense
Missense
Missense
Missense
Translocation
Missense
Translocation
Inversion
Translocation
Missense
Missense
Translocation
Missense
Missense
Missense
Missense
Missense
Deletion
Missense
Translocation
Missense
Missense
Missense
Missense
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Inversion
Missense
Translocation
Deletion
Missense
Missense
Missense
Nonsense
Missense
Missense
Translocation
Missense
Nonsense
Nonsense
Translocation
Missense
Missense
Missense
Missense
AA change
A677S
C1234G
S368L
V1042G
K988T
I853L
M201I
V1199M
E116K
T4319I
E175V
R1218W
R162H
L964V
S509R
D750G
S1269F
Q544H
T706M
Q196H
SS150>ST
F97L
E74K
S184L
R19W
Q61H
A146T
Y64D
L19F
A146T
K117N
Q61H
E63K
G13D
A146T
E180K
E285fs
C101W
A170S
G729V
R152*
S1394F
H354P
R138T
C10*
Q20*
K257N
T533N
T194I
Y354F
Sample
MMRC0191
MMRC0309
MMRC0344
MMRC0344
MMRC0344
MMRC0332
MMRC0421
MMRC0389
MMRC0408
MMRC0191
MMRC0329
MMRC0332
MMRC0286
MMRC0375
MMRC0359
MMRC0335
MMRC0191
MMRC0191
MMRC0381
MMRC0329
MMRC0343
MMRC0381
MMRC0338
MMRC0308
MMRC0381
MMRC0376
MMRC0392
MMRC0359
MMRC0191
MMRC0383
MMRC0387
MMRC0335
MMRC0335
MMRC0284
MMRC0343
MMRC0308
MMRC0389
MMRC0381
MMRC0191
MMRC0004
MMRC0282
MMRC0308
MMRC0329
MMRC0332
MMRC0338
MMRC0359
MMRC0381
MMRC0406
MMRC0408
MMRC0392
MMRC0392
MMRC0173
MMRC0383
MMRC0332
MMRC0322
MMRC0406
MMRC0173
MMRC0427
MMRC0286
MMRC0423
MMRC0376
MMRC0389
MMRC0173
MMRC0335
MMRC0191
MMRC0335
MMRC0343
MMRC0423
MMRC0335
Previously
treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
doi:10.1038/nature09837
Gene
LIPC
LIX1L
LMBR1L
LMO2
LMOD3
LNP1
LOH12CR1
LOXL2
LPO
LRIG3
LRMP
LRMP
LRMP
LRMP
LRMP
LRP1B
LRP1B
LRP1B
LRP1B
LRP1B
LRP1B
LRP2
LRP6
LRP8
LRRC16A
LRRC36
LRRC41
LRRC4C
LRRIQ3
LRRK2
LRRK2
LRRK2
LRRK2
LRRN3
LRRN3
LRTM2
LSM14A
LSM14A
LUC7L3
LUM
LY6H
LYPD4
LYST
LZTR1
MAB21L2
MACF1
MAGEC1
MAGED1
MAGED1
MAGEL2
MAN1A1
MAN1A1
MAOA
MAP1LC3B
MAP2K3
MAP2K4
MAP2K4
MAP2K4
MAP2K4
MAP2K4
MAP2K4
MAP2K4
MAP3K1
MAP3K14
MAP4K4
MAPK4
MARK2
MASP1
MATK
Chr
8
1
12
11
3
3
12
8
2
12
12
12
12
12
12
2
2
2
2
2
2
2
12
1
6
16
1
11
1
12
12
12
12
7
7
12
19
19
17
12
8
19
1
22
4
1
X
X
X
15
6
6
X
16
17
17
17
17
17
4
17
17
5
17
2
18
11
3
19
Position
(strand)
114544567(+)
144203617
47778142
33842783
69250793
101631363
12425720(+)
23235653
34043266(-)
57594383
25133277(+)
25134396
25134330
25133858(-)
25135141(+)
141586373(+)
141614994(-)
141424323
140824905
140931690
142098906(-)
169885550
12208550
53463794(+)
25689503
65941637
46523909
40093586
74421820
38918064
38994132
38953506(+)
38953703(-)
110551713
110551428
1813952
39398045
39402623
46177079
90026794
144311151
47033866
233942040
19673082
151724005
39438098(-)
140821961
51656630
51655046
21441683
119551411
119664968
43400553
85993288
21144827
8032880(+)
11890824(+)
11946633(+)
11956089(+)
33914(+)
11909171(+)
11946955(-)
56209516(-)
40720277(+)
101814695
46444433
63428833
188486521
3736123
2nd gene
C12orf11
CASC1
PRKCB
PRKCB
Chr
15
12
26958462(-)
17
53689430(+)
12
25165289(+)
16
16
2
2
18
18
18
HNF1A
DSCAM
Position
(strand)
56586588(-)
12
17
17
17
17
17
21
21
8
17
23889173(+)
23867717(+)
141707595(-)
221292668(+)
71609703(-)
53490546(-)
8522903(+)
8522979(-)
119911516(-)
11869941(-)
14883729(-)
14820955(+)
14900582(-)
11909416(-)
42321425(-)
40855018(-)
42575852(+)
40725216(-)
Type
Translocation
Missense
Missense
Missense
Missense
Missense
Long range
Missense
Translocation
Missense
Inversion
Missense
Nonsense
Translocation
Translocation
Deletion
Long range
Missense
Missense
Missense
Translocation
Missense
Missense
Deletion
Missense
Missense
Missense
Missense
Nonsense
Missense
Missense
Translocation
Translocation
Missense
Missense
Missense
Missense
Splice site
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Nonsense
Nonsense
Missense
Missense
Splice site
Missense
Missense
Missense
Long range
Long range
Long range
Long range
Translocation
Translocation
Translocation
Translocation
Deletion
Missense
Missense
Splice site
Missense
Missense
AA change
R161L
F418L
E135D
M468T
R34W
G413R
D20Y
E202Q
E180*
N1029K
F3941L
V3209A
A57V
T659I
D955Y
T53A
R403C
N278I
L46*
E155K
I1543S
S550C
Y455F
R306Q
A239T
R379_splice
I200T
Q32E
C105Y
T174I
D3289N
P172T
A125E
P369S
W380*
S68*
A767V
F526C
G234_splice
A7V
I35V
D81N
P197S
S36L
S559_splice
Y8F
R4Q
Sample
MMRC0309
MMRC0329
MMRC0383
MMRC0335
MMRC0425
MMRC0344
MMRC0421
MMRC0308
MMRC0344
MMRC0309
MMRC0344
MMRC0344
MMRC0344
MMRC0344
MMRC0344
MMRC0421
MMRC0375
MMRC0376
MMRC0425
MMRC0425
MMRC0191
MMRC0406
MMRC0028
MMRC0319
MMRC0343
MMRC0412
MMRC0028
MMRC0344
MMRC0335
MMRC0286
MMRC0344
MMRC0376
MMRC0376
MMRC0191
MMRC0322
MMRC0347
MMRC0329
MMRC0412
MMRC0322
MMRC0322
MMRC0381
MMRC0344
MMRC0028
MMRC0329
MMRC0335
MMRC0383
MMRC0356
MMRC0216
MMRC0173
MMRC0309
MMRC0322
MMRC0335
MMRC0173
MMRC0390
MMRC0421
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0344
MMRC0319
MMRC0343
MMRC0412
MMRC0359
MMRC0412
MMRC0286
Previously
treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Untreated
doi:10.1038/nature09837
Gene
MBD1
MCART1
MCF2L
MCM4
MCTP2
MCTS1
MDC1
MDM4
MDN1
ME3
MECOM
MED26
MEF2A
MEGF9
MELK
METAP2
METTL2B
METTL9
MFN1
MFSD6L
MGA
MGA
MID2
MIPEP
MKRN3
MLKL
MLL
MLL2
MLL2
MLL3
MLPH
MMP16
MMP17
MOGAT3
MON2
MOXD1
MPDZ
MPHOSPH9
MPL
MPRIP
MRC2
MRE11A
MRPL15
MRPS27
MRVI1
MSL3
MSRB3
MSRB3
MSRB3
MSRB3
MT1A
MTDH
MTDH
MTMR1
MTMR11
MTMR2
MTR
MUC16
MUC16
MUC16
MUC16
MUC17
MUC2
MUC2
MUC21
MUC6
MXRA5
MYH10
MYH10
Chr
18
9
13
8
15
X
6
1
6
11
3
19
15
9
9
12
7
16
3
17
15
15
X
13
15
16
11
12
12
7
2
8
12
7
12
6
9
12
1
17
17
11
8
5
11
X
12
12
12
12
16
8
8
X
1
11
1
19
19
19
19
7
11
11
6
11
6
17
17
Position
(strand)
46053966
37877707
112790041
49048122
92823262
119623420
30780239
202780399
90458942
85914611(-)
170697373(-)
16557098(+)
98070181
122493555
36587286
94392090
108718285(+)
21531602
180559326
8642488
39775090(+)
39784934(+)
106970865
23351435
21363470
73286702
117875341
47702190
47714190
151557958
238084372
89128127
130893124(-)
100626060
61181623
132690948
13128005
122264308(+)
43576423
16738425(-)
58107608
90023122(-)
55211768
71559926
10630174
11689608
64010867(-)
64004119(-)
63992556(+)
64013283(+)
55231284
53819616(-)
98802088(-)
149649337
148169939
95296028(+)
235053847(+)
8863576
8945925
8925540
8945158
100463930
1083295
1083094
31062393
1008462
13686616(-)
7970180(+)
8406603(+)
2nd gene
Chr
Position
(strand)
TMEM120B
12
12
19
12973435(-)
120666057(+)
18275083(-)
EHD4
EP400
MPHOSPH9
TXNRD1
TXNRD1
15
15
12
127928372(-)
39784434(-)
40032969(-)
131045475(+)
12
122273615(-)
17
16925310(+)
11
93829988(-)
12
12
12
12
122274899(+)
122264416(-)
103180160(-)
103176369(+)
8
8
98802054(+)
128868323(-)
11
1
X
17
17
134024425(-)
236285234(-)
3244036(+)
8377434( )
8377434(-)
8849242(+)
Type
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Translocation
Long range
Missense
Missense
Missense
Missense
Long range
Missense
Missense
Missense
Deletion
Deletion
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Tandem duplication
Missense
Missense
Splice site
Missense
Deletion
Missense
Tandem duplication
Nonsense
Long range
Missense
Missense
Nonsense
Missense
Long range
Long range
Long range
Long range
Missense
Long range
Long range
Missense
Missense
Long range
Long range
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Deletion
Inversion
AA change
G471A
I281V
T876M
A694V
L878V
D48Y
T1567I
Q262H
V3510M
I394M
A199V
K158R
A2S
H101Y
S85R
S226T
R105H
L171F
D483V
R152K
M2022I
H5475L
F3556S
Y987H
V112F
Y459D
E305K
L223F
G282_splice
G1384V
T49N
W606*
E85K
A206V
Q58*
E92Q
C36F
GQ210>GP
R376H
K13414E
S2297N
L7636I
G2553R
T838I
T1705I
V1638G
D154E
V1447I
Sample
MMRC0383
MMRC0390
MMRC0392
MMRC0338
MMRC0282
MMRC0406
MMRC0173
MMRC0343
MMRC0282
MMRC0383
MMRC0383
MMRC0392
MMRC0309
MMRC0406
MMRC0004
MMRC0282
MMRC0191
MMRC0286
MMRC0389
MMRC0242
MMRC0392
MMRC0332
MMRC0335
MMRC0338
MMRC0173
MMRC0387
MMRC0308
MMRC0343
MMRC0173
MMRC0242
MMRC0347
MMRC0322
MMRC0387
MMRC0173
MMRC0308
MMRC0392
MMRC0173
MMRC0335
MMRC0375
MMRC0332
MMRC0244
MMRC0338
MMRC0335
MMRC0376
MMRC0412
MMRC0332
MMRC0335
MMRC0335
MMRC0335
MMRC0335
MMRC0375
MMRC0343
MMRC0343
MMRC0244
MMRC0282
MMRC0338
MMRC0406
MMRC0319
MMRC0343
MMRC0412
MMRC0412
MMRC0392
MMRC0392
MMRC0421
MMRC0412
MMRC0329
MMRC0383
MMRC0392
MMRC0392
Previously
treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
doi:10.1038/nature09837
Gene
MYH10
MYH10
MYH10
MYH10
MYH10
MYH11
MYH11
MYH11
MYH8
MYO10
MYO18B
MYO18B
MYO1C
MYO1E
MYO3A
MYO5A
MYO6
MYO9A
MYOCD
MYOF
MYOM2
MYOM3
MYSM1
MYT1
N4BP1
NAALADL2
NALCN
NALCN
NAV2
NAV3
NAV3
NBAS
NBEA
NBN
NBPF16
NBPF3
NCAM2
NCAPD3
NCKAP1
NCLN
NCOA3
NCOR1
NCOR1
NDRG3
NDRG3
NDRG3
NDST4
NDUFA5
NDUFAF2
NEB
NEB
NEBL
NEBL
NEDD1
NEFH
NEFM
NES
NEURL4
NFATC3
NFIA
NFIB
NID1
NKAIN2
NKAIN2
NKAIN3
NKAIN3
NKAPL
NLRP2
NLRP4
Chr
17
17
17
17
17
16
16
3
17
5
22
22
17
15
10
14
6
15
17
10
8
1
1
20
16
3
13
13
11
12
12
2
13
8
1
1
21
11
2
19
20
17
17
20
20
20
4
7
5
2
2
10
10
12
22
8
1
17
16
1
9
1
2
2
8
8
6
19
19
Position
(strand)
8325800(+)
8413251(+)
8348738
8415436(-)
8406802(+)
15765375(+)
15779710(+)
77792962(-))
77792962(
10244725
16754269
24730698
24577473
1329657
57437976(+)
26522184
95299060(+)
76614846(+)
69957446
12581699(+)
95073029
2064591
24261151
58920143
62341567
47134504
176237088(+)
100744950(+)
100734313
20034002
76924973
76912769
15224765
35118474
91018479
147023078
21679254
21760803
133595759
183601903(+)
3143630
45714618
15910721(-)
8172996(-)
34726791(+)
34766752(+)
34757479(+)
116064910(+)
122969429
60385870(+)
152092285
152289034
21160467
21187262
95835636
28215638
24830678
154910509(-)
7170770
66806021(-)
61435759(+)
14234848(-)
234278803
35385997(+)
35460209(-)
51306139(-)
56102765(+)
28335421
60186564(+)
61061928
2nd gene
NCOR1
PIGL
PDE9A
RICH2
THSD7A
ITGBL1
Chr
17
17
Position
(strand)
15891328(-)
16077806(-)
21
21
16
16
16
42325724(-)
42952931(-)
15773834(+)
34645650(+)
15799932(+)
15
57475211(+)
15
6
50550021(-)
77319167(-)
17
12716278(-)
7
13
11574366(+)
101001082(-)
70370171(+)
PIGL
17
17
20
20
20
4
16070205(-)
15909891(+)
34733246(-)
34771458(+)
48734587(-)
116233317(-)
BAG4
38173841(+)
CDH1
VAV3
C12orf42
154942931(+)
16
1
12
67347328(+)
108178920(-)
102325833(-)
6
6
8
8
124531546(+)
124551124(-)
63764015(+)
63763970(-)
19
60187365(+)
Type
Long range
Long range
Missense
Translocation
Translocation
Inversion
Long range
Translocation
Missense
Missense
Missense
Missense
Missense
Inversion
Nonsense
Translocation
Deletion
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Deletion
Missense
Missense
Missense
Missense
Nonsense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
In frame deletion
Inversion
Long range
Deletion
Inversion
Long range
Deletion
Nonsense
Translocation
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Tandem duplication
Missense
Tandem duplication
Long range
Translocation
Missense
Translocation
Translocation
Long range
Long range
Missense
Inversion
Missense
AA change
R1169C
E1148Q
A1079P
I2116N
R1271Q
N298K
R1495*
T1974P
R1770Q
Y1255C
T1269M
Q387H
M1035T
A835T
P369H
R1585Q
K508N
K243E
W2325*
W2325
A2566T
V729L
L595V
D444E
V554F
I46L
M116T
M1336_S1337>M
Q111*
P5553S
A200T
V501M
D272E
R113Q
V670E
M93L
D359G
D112G
R98H
V453M
Sample
MMRC0392
MMRC0392
MMRC0390
MMRC0392
MMRC0392
MMRC0344
MMRC0344
MMRC0191
MMRC0421
MMRC0335
MMRC0335
MMRC0344
MMRC0338
MMRC0344
MMRC0028
MMRC0335
MMRC0421
MMRC0286
MMRC0191
MMRC0242
MMRC0427
MMRC0338
MMRC0387
MMRC0347
MMRC0392
MMRC0406
MMRC0332
MMRC0242
MMRC0322
MMRC0412
MMRC0427
MMRC0427
MMRC0412
MMRC0338
MMRC0344
MMRC0329
MMRC0335
MMRC0173
MMRC0309
MMRC0308
MMRC0004
MMRC0392
MMRC0392
MMRC0387
MMRC0412
MMRC0387
MMRC0421
MMRC0308
MMRC0344
MMRC0376
MMRC0173
MMRC0319
MMRC0421
MMRC0286
MMRC0390
MMRC0335
MMRC0242
MMRC0390
MMRC0425
MMRC0408
MMRC0191
MMRC0390
MMRC0421
MMRC0421
MMRC0344
MMRC0344
MMRC0191
MMRC0383
MMRC0338
Previously
treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
doi:10.1038/nature09837
Gene
NLRP7
NLRP7
NLRP8
NLRP8
NNT
NOLC1
NOM1
NOS1
NOTCH2NL
NOTCH4
NPAS3
NPFFR2
NPLOC4
NPR2
NPY2R
NR2F2
NR3C2
NR3C2
NR6A1
NRAS
NRAS
NRAS
NRAS
NRAS
NRAS
NRAS
NRAS
NRAS
NRG1
NRG3
NRG3
NRP2
NRXN1
NRXN1
NRXN3
NRXN3
NRXN3
NRXN3
NRXN3
NRXN3
NSMCE2
NSMCE2
NSMCE2
NSUN2
NT5C3L
NTM
NTN1
NTN1
NTN1
NTN1
NTN1
NTN1
NTN1
NTN1
NTN1
NTN1
NUCB2
NUMA1
NUMB
NUP155
NUP155
NUP160
NUP210
NUP210L
NUP214
NUP93
OBFC2A
OBSCN
OCM
Chr
19
19
19
19
2
10
7
12
1
6
14
4
17
9
4
15
4
4
9
1
1
1
1
1
1
1
1
1
8
10
10
2
2
2
14
14
14
14
14
14
8
8
8
5
17
8
17
17
17
17
17
17
17
17
17
17
3
11
14
5
5
11
3
1
9
16
2
1
7
Position
(strand)
60104250(+)
60135655(-)
61157859
61159220
216780312(+)
103902447(+)
156439605
116194635
143964034(-)
32299637
33332866
73116661
77184284
35784002
156355623
94681737
149400600
149254800
126511745(+)
115058052
115058051
115058053
115058052
115058052
115058052
115058052
115060268
115060268
32740315
84384775(+)
84734905
206336664
50256599(-)
50317592
78821969(+)
79100435(+)
78959852(-)
78825766(-)
78947069(-)
79101780(-)
126438008(+)
126386631(+)
126387784(+)
6664174
37238614
41188158(-)
8874232(-)
8931037(-)
8962987(+)
9053236(+)
8849351(-)
8889896(-)
8930086(+)
9003033(+)
8929539(-)
8931346(+)
124191567(-)
71407199
72813619
37353901
37387135
47448402(+)
13402852
152328606
133004531
55425591
192257253
226498862
5887105
2nd gene
SMPD3
LCLAT1
Chr
19
X
5
16
11
10
GAS7
MAP2K4
MAP2K4
BACE2
DSCAM
FAM3B
Position
(strand)
60135890(-)
136757206(-)
43687830(-)
66962164(-)
30594834(-)
9633987(-)
84709572(-)
70640059(+)
14
14
14
14
14
14
8
8
8
79079626(-)
79211468(-)
79205866(-)
78956817(+)
79057415(+)
79201916(+)
126454670(-)
128775537(-)
128834720(+)
11
17
17
17
17
17
21
21
21
21
21
11
11
130987563(+)
9062733(-)
9776265(-)
11890893(-)
11958316(-)
8899501(+)
42308631(+)
42444746(+)
41530729(+)
40864782(-)
41629575(-)
17306312(+)
47793673(-)
Type
Deletion
Translocation
Missense
Missense
Translocation
Translocation
Missense
Missense
Translocation
In frame deletion
Missense
Missense
Splice site
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Deletion
Missense
Missense
Long range
Missense
Deletion
Deletion
Inversion
Tandem duplication
Tandem duplication
Tandem duplication
Deletion
Long range
Long range
Missense
Missense
Translocation
Inversion
Inversion
Long range
Long range
Tandem duplication
Translocation
Translocation
Translocation
Translocation
Translocation
Translocation
Missense
Missense
Missense
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Missense
Missense
AA change
I208T
V662I
L387Q
Y593H
L15_L16>L
G389V
R60Q
K177_splice
G259R
K361R
S223L
F626C
E785K
Q61R
Q61H
Q61K
Q61R
Q61R
Q61R
Q61R
G13R
G13R
H433N
N552T
L689R
S94C
F374L
H166P
I251L
S448L
P751S
T213P
P247L
H759P
E350K
R530W
T144K
G1150C
R20Q
Sample
MMRC0383
MMRC0383
MMRC0028
MMRC0392
MMRC0191
MMRC0390
MMRC0425
MMRC0392
MMRC0191
MMRC0319
MMRC0356
MMRC0359
MMRC0389
MMRC0282
MMRC0344
MMRC0389
MMRC0308
MMRC0319
MMRC0387
MMRC0244
MMRC0284
MMRC0319
MMRC0343
MMRC0383
MMRC0390
MMRC0412
MMRC0423
MMRC0173
MMRC0425
MMRC0392
MMRC0329
MMRC0390
MMRC0309
MMRC0322
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0343
MMRC0392
MMRC0389
MMRC0427
MMRC0412
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0191
MMRC0309
MMRC0389
MMRC0191
MMRC0309
MMRC0408
MMRC0344
MMRC0332
MMRC0286
MMRC0376
MMRC0376
MMRC0338
MMRC0389
Previously
treated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Treated
doi:10.1038/nature09837
Gene
ODF1
ODZ1
ODZ2
ODZ4
OLFM3
OPRL1
OR12D2
OR1G1
OR1L6
OR2A14
OR2G2
OR2K2
OR2L8
OR4D5
OR4E2
OR4K14
OR5AP2
OR5D16
OR5H14
OR5P3
OR8D1
OR8J3
OR8K3
ORAOV1
OSBP
OSBP2
OSBPL6
OSBPL8
OSR2
OVCH1
PAK4
PANK3
PAPPA2
PARK2
PARN
PARN
PARVG
PBK
PBRM1
PBX2
PCCA
PCDH10
PCDH10
PCDH15
PCDH17
PCDH18
PCDH18
PCDH20
PCDH7
PCDHA11
PCDHA12
PCDHB1
PCDHB10
PCDHB13
PCDHGA7
PCYT1B
PDE11A
PDE11A
PDE3A
PDE4D
PDE8B
PDGFRL
PDIA6
PDZD8
PFAS
PFAS
PFAS
PFAS
PFAS
Chr
8
X
5
11
1
20
6
17
9
7
1
9
1
11
14
14
11
11
3
11
11
11
11
11
11
22
2
12
8
12
19
5
1
2
16
16
22
8
3
6
13
4
4
10
13
4
4
13
2
5
5
5
5
5
5
X
2
2
12
4
5
8
2
10
17
17
17
17
17
Position
(strand)
103642209
123633315
167421693
78161592(+)
102042783
62194608
29472995
2977247
124552015
143458045
245818830
113129840
246179310
123315982
21203812
19552945
56165605
55363092
99351494
7803897
123684960
55661718
55843058
69191913
59100733
29613453
178934702
75308492
100030520
29489537
44356290
167921011
174887833(+)
34866613(-)
11675607(-)
14557020
42923414
27724445
52662877(+)
32263038
99946892(+)
134303621
134293320
55452774
57105459
138670955
138672160
60884812
172845896(-)
140230230
140235327
140412416
140552936
140576140
140743885
24503217
178644936
178253862
20681341
96913100(-)
76682659
17530561
10854709
119124316
8105431(-)
7936725(-)
8110065(-)
8112256( )
8112256(-)
8105593(+)
2nd gene
Chr
Position
(strand)
11
78567574(-)
6
6
16
38796456(+)
161858558(-)
14557118(+)
KRT15
17
36924674(+)
NALCN
13
100666583(-)
MAP2K4
MYH10
DSCAM
17
17
17
21
21
30588059(-)
59410132(+)
11947091(-)
8110682(+)
8376370(+)
39868238(+)
40855116(-)
Type
Missense
Missense
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Missense
Nonsense
Missense
Missense
Missense
Nonsense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Translocation
Long range
Missense
Missense
Missense
Translocation
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
Missense
Missense
Long range
Tandem duplication
Tandem duplication
Translocation
Translocation
AA change
N225S
L356Q
G454C
D326Y
L31V
K180N
V117F
Q23R
A303T
C182*
G232V
F176L
V150G
R226*
I83T
Y296C
S97P
S192F
A67S
L305V
S18C
Q234E
F92L
E773Q
R383Q
E401Q
D294N
T55M
T941I
S300T
I301F
G437V
N210K
M241L
G328A
A946V
G859C
T809A
T260A
A580T
A178V
P474R
A453V
G29V
V393L
S209R
C754Y
R412Q
R265K
R159W
F537L
N681I
V344G
Y264F
P99S
R138H
Sample
MMRC0284
MMRC0387
MMRC0383
MMRC0319
MMRC0389
MMRC0381
MMRC0329
MMRC0356
MMRC0344
MMRC0421
MMRC0356
MMRC0387
MMRC0191
MMRC0425
MMRC0392
MMRC0376
MMRC0282
MMRC0309
MMRC0309
MMRC0412
MMRC0381
MMRC0344
MMRC0282
MMRC0244
MMRC0389
MMRC0242
MMRC0309
MMRC0389
MMRC0191
MMRC0335
MMRC0329
MMRC0242
MMRC0309
MMRC0376
MMRC0344
MMRC0344
MMRC0383
MMRC0335
MMRC0335
MMRC0284
MMRC0392
MMRC0343
MMRC0381
MMRC0376
MMRC0412
MMRC0344
MMRC0173
MMRC0335
MMRC0191
MMRC0381
MMRC0216
MMRC0412
MMRC0390
MMRC0329
MMRC0191
MMRC0191
MMRC0242
MMRC0329
MMRC0347
MMRC0309
MMRC0004
MMRC0338
MMRC0338
MMRC0329
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
Previously
treated
Untreated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
doi:10.1038/nature09837
Gene
PFAS
PFTK1
PFTK2
PGM2L1
PHACTR2
PHC1
PHTF1
PICK1
PIGK
PIGL
PIGL
PIGL
PIGL
PIGL
PIGL
PIGZ
PIWIL1
PKD1L1
PKHD1
PKHD1
PKHD1
PKHD1
PKHD1L1
PKHD1L1
PKP1
PLA2G2D
PLA2G2D
PLA2G2E
PLA2G6
PLA2R1
PLCB4
PLD2
PLEKHA2
PLEKHA7
PLEKHG2
PLK1S1
PLK4
PLLP
PMP22
PMP22
PNLIP
PNPLA3
PNRC1
PNRC1
PODN
POLE
POLH
POLQ
POLR1C
POLR3A
POLR3C
POLR3G
PON3
POT1
PPAP2A
PPFIA1
PPFIA4
PPFIBP1
PPP1R12B
PPRC1
PPRC1
PPTC7
PRDM1
PRDM1
PRG4
PRICKLE2
PRIM2
PRIMA1
PRKAG2
Chr
17
7
2
11
6
12
1
22
1
17
17
17
17
17
17
3
12
7
6
6
6
6
8
8
1
1
1
1
22
2
20
17
8
8
19
20
4
15
17
17
10
22
6
6
1
12
6
3
6
10
1
5
7
7
5
11
1
12
1
10
10
12
6
6
1
3
6
14
7
Position
(strand)
8111022(-)
90338499(+)
202375229(+)
73762831(-)
144169914
8974433
114085790(+)
36789806(-))
36789806(
77399662
8067247(+)
8193111(-)
8208481(-)
16070378(+)
16107242(+)
16109115(-)
198158711
129408041
47496004(-)
1322688(-)
51693456(+)
51592193
52018871
110546210
110536259
199556104
20315541
20314693
20121737
36842102
160542111
9336667
4668580
38946121
52121898(+)
44604700
21154716(+)
129031759
50379143(-)
8857645(-)
15075518(+)
118308665
42673444
89847473
89847360
53320264
131730180
43689516
122684928
43595460
79455508
144305508
89838223
94854641(+)
124286335
54779768(+)
69878106
201291220
27732507
200661436
103897851(+)
103897926(-)
109468207
106661791
106661497
184543900
64108038
57537913(-)
93272541(+)
151109276
2nd gene
SH3BGR
PTP4A3
DSCAM
SLC37A1
SLC37A1
Chr
21
7
2
11
8
22
142501723(+)
38770891(+)
17
17
17
21
21
21
16149713(-)
16138288(+)
16070121(+)
40918883(+)
42834123(+)
42834251(-)
7
6
6
DSCAM
NDUFAF2
NEURL
ZDHHC1
Position
(strand)
39805530(-)
90399548(-)
202389723(-)
73765908(+)
47846579(+)
51697366(+)
76546987(+)
11
16790987(-)
20
21201650(-)
16
17
21
55866315(+)
15084210(-)
40854640(+)
12
37672207(-)
60346427(+)
10
16
7
14
105267915(-)
65992199(+)
30116221(-)
93301882( )
93301882(-)
Type
Translocation
Deletion
Deletion
Tandem duplication
Missense
Missense
Translocation
Long range
Missense
Long range
Long range
Long range
Translocation
Translocation
Translocation
Missense
Missense
Tandem duplication
Long range
Long range
Missense
Missense
Missense
Splice site
Missense
Missense
Nonsense
Missense
Missense
Nonsense
Missense
Nonsense
Missense
Translocation
Missense
Deletion
Missense
Translocation
Long range
Translocation
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Long range
Missense
Missense
Missense
Missense
Long range
Translocation
Missense
In frame deletion
Missense
Missense
Missense
Translocation
Deletion
Missense
AA change
F545I
V250L
A240V
V485G
D552V
R3957H
Y828N
K2658R
G2292_splice
C461S
Q19H
W62*
G47S
Y602C
Y777*
A572D
S648*
S648
S314C
P537A
E631D
F314L
S432Y
D47fs
E10K
S610F
V1444L
K462N
P1989S
N96K
D66H
I471V
E187D
G205D
E739K
A117T
A794T
L221F
N155H
A739_V754del
S641R
G809E
R390W
M121L
Sample
MMRC0392
MMRC0356
MMRC0343
MMRC0319
MMRC0329
MMRC0309
MMRC0421
MMRC0375
MMRC0356
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0216
MMRC0390
MMRC0356
MMRC0389
MMRC0389
MMRC0309
MMRC0347
MMRC0343
MMRC0338
MMRC0319
MMRC0412
MMRC0242
MMRC0244
MMRC0329
MMRC0242
MMRC0308
MMRC0389
MMRC0389
MMRC0191
MMRC0356
MMRC0421
MMRC0329
MMRC0383
MMRC0392
MMRC0392
MMRC0387
MMRC0286
MMRC0286
MMRC0286
MMRC0421
MMRC0309
MMRC0359
MMRC0389
MMRC0383
MMRC0376
MMRC0356
MMRC0392
MMRC0242
MMRC0242
MMRC0344
MMRC0389
MMRC0191
MMRC0242
MMRC0421
MMRC0390
MMRC0390
MMRC0284
MMRC0309
MMRC0282
MMRC0383
MMRC0387
MMRC0191
MMRC0332
MMRC0389
Previously
treated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
doi:10.1038/nature09837
Gene
PRKCB
PRKCB
PRKCZ
PRKD2
PRKD3
PRKDC
PRKG1
PRPF38B
PRPF8
PRR21
PRR4
PRSS16
PRSS16
PRSS22
PRSS45
PRUNE2
PSEN1
PSMC6
PSMD1
PTDSS1
PTK2
PTK2
PTPLA
PTPN11
PTPRD
PTPRG
PUS7
PUS7L
QRICH2
RAB25
RAB27B
RAB28
RAB2A
RAB3GAP1
RAB5B
RABL3
RAD54L2
RAG1
RAG2
RALGAPA1
RALGAPA2
RALGAPB
RALGPS1
RALYL
RALYL
RANBP17
RANBP3L
RANBP9
RAP1GAP2
RAP1GAP2
RASAL2
RASAL2
RASGRF1
RB1
RBKS
RBM25
RBM33
RBM33
RBM39
RBM5
RBM9
RBM9
RBMS3
RBP4
RC3H1
RCOR1
RD3
RDH16
RELN
Chr
12
12
1
19
2
8
10
1
17
2
12
6
6
16
3
9
14
14
2
8
8
8
10
12
9
3
7
12
17
1
18
4
1
2
12
3
3
11
11
14
20
20
9
8
8
5
5
6
17
17
1
1
15
13
2
14
7
7
20
3
22
22
3
10
1
14
1
12
7
Position
(strand)
24644411(+)
24646241(-)
2056602
51885761
37350314
48869437
52873989(+)
109042827
1503632
240630178
11022945(+)
27331050
27331057
2843909
46761162
78457362
72739859(+)
52254707
231738241
97376525
126684555(-)
127893075(+)
17676236
111411271
8661723(+)
62253880
104910053
42434859
71800016
154304773
50695888
12992253
100586426(-)
135636644
54667069
121907629
51628225(-)
36554291
36572180
35194796
20433355(-)
36635398(+)
128997310
83529322(+)
83664628(-)
170600740
36307144
13749808(+)
2691527(-)
2711029(+)
176483017(+)
176460940(-)
77110902
47937490
27925174(-)
72647499
155186794(+)
155186274
33760560
50126409
34315726(+)
28567428(-)
29960341(+)
95343722
172187745
102220649(+)
209721280
55635173
103177146
2nd gene
Chr
16
16
10
ETV6
TDRD9
12
14
8
8
FAM19A5
ZC3H7B
TRAF3
Position
(strand)
23905687(-)
23880041(-)
52904191(-)
11854448(-)
103564330(-)
141913260(+)
141913284(-)
9161382(-)
61652655(-)
66857717(+)
21
20
9840160(-)
37118142(-)
8
8
85616029(+)
85606481(-)
6
20
20
6
22
13781392(-)
31926923(+)
31915944(-)
85586756(-)
47448413(-)
95015910(-)
155286244(-)
22
22
22
14
34572420(-)
34692913(-)
40052405(-)
102424705(-)
Type
Translocation
Translocation
Missense
Missense
Missense
Missense
Deletion
Missense
Missense
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Long range
Missense
Missense
Long range
Long range
Missense
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
Missense
Long range
Missense
Nonsense
Missense
Translocation
Deletion
Missense
Long range
Long range
Missense
Missense
Deletion
Translocation
Translocation
Translocation
Translocation
Missense
Missense
Translocation
Missense
Deletion
Missense
Missense
Missense
Deletion
Long range
Translocation
Missense
Splice site
Deletion
Missense
Missense
Missense
AA change
Y126D
I425T
Q575H
S3546F
W213R
K2108M
P299S
S508G
I510T
M225I
V30L
A2805V
S215N
E855D
V155fs
L253R
G503V
Q1399R
Q331K
E153Q
I630T
L110F
F25C
G152V
L780Q
Q20E
L97F
G954D
R39*
E1316K
G344S
S876G
F40I
P386H
M825K
T634S
S205L
A409T
W547L
R139H
M841_splice
T34M
T119M
D207N
Sample
MMRC0344
MMRC0344
MMRC0322
MMRC0376
MMRC0338
MMRC0389
MMRC0191
MMRC0308
MMRC0389
MMRC0308
MMRC0332
MMRC0329
MMRC0329
MMRC0343
MMRC0376
MMRC0173
MMRC0335
MMRC0308
MMRC0375
MMRC0332
MMRC0343
MMRC0343
MMRC0242
MMRC0387
MMRC0332
MMRC0375
MMRC0412
MMRC0347
MMRC0375
MMRC0347
MMRC0329
MMRC0329
MMRC0383
MMRC0322
MMRC0329
MMRC0383
MMRC0344
MMRC0347
MMRC0376
MMRC0286
MMRC0191
MMRC0392
MMRC0383
MMRC0421
MMRC0421
MMRC0216
MMRC0309
MMRC0191
MMRC0387
MMRC0387
MMRC0191
MMRC0309
MMRC0338
MMRC0329
MMRC0343
MMRC0383
MMRC0356
MMRC0356
MMRC0322
MMRC0173
MMRC0392
MMRC0392
MMRC0343
MMRC0375
MMRC0387
MMRC0319
MMRC0308
MMRC0284
MMRC0421
Previously
treated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Treated
doi:10.1038/nature09837
Gene
REPS1
RERE
RETSAT
RFX1
RGL1
RGNEF
RIMS2
RIMS2
RIPK4
RMI1
RNASEN
RNF168
RNF19A
RNF213
RNF26
ROBO2
ROBO2
ROPN1
RORB
RPA4
RPGR
RPL10
RPS6KA1
RRM1
RRN3
RTCD1
RTN1
RUFY2
RUNDC3B
RUNDC3B
RWDD2A
RXFP1
RXFP2
RYR1
RYR2
RYR3
RYR3
S100PBP
SACM1L
SAMD13
SAMHD1
SAMHD1
SART1
SCG5
SCGB1A1
SCN10A
SCN11A
SCN2A
SCYL2
SDF2
SDR16C5
SEC13
SEC14L2
SEC14L5
SEC63
SEL1L3
SEMA3A
SEMA3E
SEMG1
SENP1
SEPT14
SERPINB3
SERPINB6
SERPINE2
SERPINH1
SERTAD4
SETBP1
SETD2
Chr
6
1
2
19
1
5
8
8
21
9
5
3
8
17
11
3
3
3
9
X
X
X
1
11
16
1
14
3
7
7
6
4
13
19
1
15
15
1
3
1
20
20
11
15
11
3
3
2
12
17
8
3
22
16
6
4
7
7
20
12
7
18
6
2
11
1
18
3
Position
(strand)
139311624(+)
8494310(-)
85424368
13940433
182162007
73081472
104967063
105056901
42034912
85807333
31485209
197714230
101340094
75931631
118712253
77709336
77696952
125178495
76470227
96026003
38030561
153281344
26754634
4113032
15077660(+)
100506393
59282905
12692826(-)
87190924(+)
87190950(-)
83962573
159787750
31254863
43688832
235881425
31805910
31627672
33094122
45760070
84587998
34989013
34989043
65502882
30776098
61946352
38805490
38867004
165918977
99253596
24000392
57377504(-)
10317980(-)
29141994
4969295(-)
108357369
25378497
83430493
82885676
43269993
46726474
55869681
59475182
2900828
224548839
74955575
208481863
40785677
47138966
2nd gene
Chr
18
8
16
RB1
RB1
10
13
13
Position
(strand)
50712621(+)
57670917(+)
26381218(-)
69806115(+)
47872217(-)
47872099(+)
CD300LD
10
17
4626076(+)
70089089(-)
SDK2
17
69031684(+)
Type
Translocation
Translocation
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Nonsense
Missense
Long range
Missense
Missense
Translocation
Translocation
Translocation
Missense
Nonsense
Nonsense
Missense
Splice site
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Translocation
Missense
Translocation
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Nonsense
AA change
A533V
P559L
K790N
A30P
R354W
P973L
Q504K
T538S
N919K
L71H
I795V
E2081K
C404F
S737G
R614C
G47E
C299F
S13Y
E879K
E66G
Q283*
N716H
E82K
S97T
E248Q
S568*
S568
S303*
A2864V
K2608_splice
R2315H
W264R
R375C
G557R
H88Y
E228Q
D218H
V769M
E211A
E47T
C144F
D1433E
L983F
N642I
E126D
Q277K
C56Y
S908L
W608C
F172L
H214P
D601H
S217R
Q211K
K81E
N407Y
A178V
V210A
P792A
Q722*
Q722
Sample
MMRC0335
MMRC0191
MMRC0191
MMRC0381
MMRC0319
MMRC0242
MMRC0332
MMRC0389
MMRC0347
MMRC0343
MMRC0412
MMRC0343
MMRC0387
MMRC0389
MMRC0309
MMRC0216
MMRC0319
MMRC0322
MMRC0347
MMRC0356
MMRC0338
MMRC0282
MMRC0335
MMRC0425
MMRC0344
MMRC0286
MMRC0375
MMRC0356
MMRC0421
MMRC0421
MMRC0389
MMRC0343
MMRC0347
MMRC0322
MMRC0389
MMRC0242
MMRC0412
MMRC0381
MMRC0309
MMRC0335
MMRC0282
MMRC0282
MMRC0347
MMRC0412
MMRC0282
MMRC0347
MMRC0191
MMRC0389
MMRC0308
MMRC0338
MMRC0343
MMRC0421
MMRC0242
MMRC0421
MMRC0376
MMRC0389
MMRC0216
MMRC0242
MMRC0408
MMRC0191
MMRC0343
MMRC0329
MMRC0191
MMRC0425
MMRC0392
MMRC0390
MMRC0308
MMRC0319
Previously
treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Untreated
Untreated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
doi:10.1038/nature09837
Gene
SETD4
SETX
SF3A3
SFMBT1
SFRP4
SFRP4
SFTPD
SFXN4
SGCZ
SGCZ
SH2D2A
SHANK2
SHISA6
SHISA6
SHKBP1
SHOC2
SHROOM2
SI
SI
SI
SIAH3
SIGLEC1
SIPA1
SIPA1L2
SIX1
SKIV2L2
SKP2
SLC10A7
SLC12A2
SLC14A1
SLC16A9
SLC17A4
SLC1A5
SLC1A5
SLC1A7
SLC23A2
SLC25A13
SLC26A4
SLC27A5
SLC27A5
SLC2A5
SLC35C1
SLC35F3
SLC37A1
SLC38A9
SLC45A4
SLC4A5
SLC5A12
SLC6A12
SLC8A3
SLC9A3R1
SLC9A5
SLC9A6
SLCO1B3
SLCO2A1
SLITRK2
SLITRK4
SLITRK6
SLMAP
SMAP2
SMARCB1
SMARCC1
SMC5
SMC5
SMEK1
SMOC2
SMOX
SMPDL3A
SNAP25
Chr
21
9
1
3
7
7
10
10
8
8
1
11
17
17
19
10
X
3
3
3
13
20
11
1
14
5
5
4
5
18
10
6
19
19
1
20
7
7
19
19
1
11
1
17
5
8
2
11
12
14
17
16
X
12
3
X
X
13
3
1
22
3
9
9
14
6
20
6
20
Position
(strand)
36339866
134129739
38222466
52978163
37922289
37913675
81696391
120902700(+)
15134428(+)
14517910(+)
155050293
69976211(+)
8032858(+)
11118073(-)
45781433
112757286
9874732
166233893
166208477
166182883
45285451(-)
3622990
65173679
230709105(-)
60183029
54717998(-)
36219832
147583367
127477875
41401542(+)
61094075
25878738(-)
51972473
51973890
53330870
4814509
95613829
107102699
63701835
63702771
9029487(-)
45789155
232390531(+)
8859523(+)
55010931(+)
136489024(-)
74303586
26661948
176245
69703977
70276277
65843898(-)
134932475
20905295
134296237(-)
144711747
142546379
85266568
57825386
40653559
22464037
47297417(-)
72083263
72102771
91006961
168687183
4111429
123166517
10225646
2nd gene
Chr
Position
(strand)
IL1RAPL2
KIF13B
23
8
10
104703794(+)
29107152(-)
44054930(+)
11
17
17
70022000(+)
11114064(+)
14865882(-)
13
CDC25C
MAP3K3
61419069(+)
230748579(+)
137687474(+)
18
41562328(-)
19
52519405(-)
11
59089279(-)
7
21
5
8
44883921(-)
42834577(+)
55155068(-)
142304138(-)
17
59078175(-)
135161012(+)
47610784(+)
Type
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Long range
Translocation
Inversion
Long range
Long range
Missense
Missense
Missense
Missense
Missense
Missense
Long range
Missense
Missense
Tandem duplication
Missense
Long range
Missense
Missense
Missense
Deletion
Missense
Translocation
Missense
Missense
Missense
Nonsense
Missense
Missense
Missense
Missense
Translocation
Missense
Translocation
Translocation
Deletion
Long range
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
Tandem duplication
Nonsense
Missense
Missense
Missense
Missense
Tandem duplication
Missense
Missense
Missense
Missense
Missense
Missense
Missense
AA change
V204I
H2581L
D144Y
D8N
D126N
K324N
L2R
E162fs
A379T
Q390R
R1536G
T850I
M1395L
T1753S
V1045G
P866Q
N194Y
C399G
L151F
I317L
G118R
C363Y
A314T
I325M
R177*
D476G
T225K
M644I
V523L
S263N
P1099L
G414S
W380C
G306R
D322H
R440K
Q146R
K38*
K38
L71fs
P693T
I346M
N200K
I63T
E194K
N375D
A532T
E165K
V382I
Y193F
R119C
Sample
MMRC0344
MMRC0244
MMRC0173
MMRC0381
MMRC0381
MMRC0406
MMRC0322
MMRC0309
MMRC0421
MMRC0421
MMRC0308
MMRC0421
MMRC0392
MMRC0392
MMRC0322
MMRC0406
MMRC0347
MMRC0284
MMRC0375
MMRC0406
MMRC0392
MMRC0028
MMRC0389
MMRC0344
MMRC0173
MMRC0344
MMRC0282
MMRC0389
MMRC0425
MMRC0319
MMRC0383
MMRC0191
MMRC0375
MMRC0387
MMRC0338
MMRC0412
MMRC0425
MMRC0381
MMRC0286
MMRC0308
MMRC0191
MMRC0359
MMRC0383
MMRC0392
MMRC0421
MMRC0421
MMRC0173
MMRC0329
MMRC0412
MMRC0421
MMRC0286
MMRC0425
MMRC0389
MMRC0427
MMRC0383
MMRC0322
MMRC0387
MMRC0309
MMRC0308
MMRC0381
MMRC0282
MMRC0344
MMRC0286
MMRC0322
MMRC0383
MMRC0387
MMRC0322
MMRC0319
MMRC0338
Previously
treated
Treated
Untreated
Treated
Untreated
Untreated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Untreated
Untreated
Untreated
doi:10.1038/nature09837
Gene
SNAP47
SNAPC3
SNTB2
SNTG2
SNX15
SNX19
SOBP
SOCS2
SOHLH2
SORCS2
SP100
SP140
SP8
SPATA17
SPATS2
SPDYE1
SPEF2
SPEG
SPOCK1
SPOP
SPRED1
SPTA1
SPTBN1
SRD5A3
SRRM1
SRRM2
SSX4
ST13
ST14
ST18
ST3GAL3
ST5
ST7
STAB2
STAC
STAG1
STARD8
STAT2
STK17A
STK38L
STK4
STRN3
STX8
SULT2B1
SVIL
SVIL
SVIL
SYDE2
SYNE2
SYNJ1
SYT17
SYT3
SYTL2
TAAR8
TAC4
TACR3
TADA2A
TAGAP
TAPBPL
TAS2R38
TBC1D1
TBC1D9
TCERG1L
TECPR1
TEPP
TET1
TET1
TEX2
TFAM
Chr
1
9
8
2
11
11
6
12
13
4
2
2
7
1
2
7
5
2
5
17
15
1
2
4
1
16
X
13
11
8
1
11
7
12
3
3
X
12
7
12
20
14
17
19
10
10
10
1
14
21
4
19
11
6
17
4
17
6
12
7
4
4
10
7
16
10
10
17
10
Position
(strand)
226021352
15441331
108036097(-)
1253754
64559001
130278478
108061474
92492809
35645870
7749870
230693320(-)
230842889
20791710
216085951(-)
11711670(+)
44013468
35487987(-)
220062795
136431326
45051467
36430666
156876080
54709582
55920272
24850690
2752059
48129002
71857552(+)
129564854
53289361
44136263(+)
8708638
116592004(+)
102588022(+)
36501488
137673970
67859013
55034851
43614462
27342037
43137104
30457961
9219719(+)
53782366
29810637
29861680
29855698(-)
85416527
63695234
32933263
87142950(+)
55821002
85114687
132916334
45280282
104860263
32857793
159377187
6414085(-)
141319243
37800191(-)
141809523
132834859
97708386
56569422
70096986
70096858
59613101( )
59613101(-)
59824131
2nd gene
Chr
Position
(strand)
16
67821681(-)
KLHL14
18
12
28583975(+)
48193920(-)
35733151(-)
22
RASAL3
MTM1
39578062(+)
23
61647996(-)
19
23
15434289(+)
149582976(-)
17
RNF169
231008958(-)
11
16
14654365(-)
74209206(-)
19128527(-)
12
6433311(+)
13
80893772(-)
17
59840409(+)
Type
Missense
Missense
Translocation
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Inversion
Missense
Missense
Translocation
Translocation
Missense
Inversion
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
Translocation
Missense
Translocation
Translocation
Missense
Missense
Missense
Missense
Nonsense
Missense
Missense
Missense
Long range
Missense
Missense
Missense
Translocation
Missense
Missense
Translocation
Missense
Missense
Nonsense
Missense
Missense
Missense
Missense
Tandem duplication
Missense
Translocation
Nonsense
Missense
Missense
Missense
Missense
Missense
Tandem duplication
Missense
AA change
H398R
S249L
L372M
E121D
E819K
R245G
D107G
S320Y
I546N
S474T
S84F
R237C
E2937D
P189L
S119R
F282I
M1632I
P603A
Y75C
S242N
S510F
S42F
V151I
E4K
R259W
R169C
I394V
L787M
N204S
R168*
H39Q
K446R
T401I
V80M
A1661V
R541H
R854Q
E5311Q
F1286fs
S456T
T154N
W270*
E33Q
A7S
E33K
T441K
L239Q
S529*
H363Q
L255P
Q122H
H1547P
Q1504H
L182P
Sample
MMRC0216
MMRC0389
MMRC0344
MMRC0390
MMRC0191
MMRC0356
MMRC0329
MMRC0425
MMRC0004
MMRC0335
MMRC0242
MMRC0344
MMRC0308
MMRC0343
MMRC0375
MMRC0425
MMRC0335
MMRC0389
MMRC0244
MMRC0421
MMRC0387
MMRC0412
MMRC0383
MMRC0392
MMRC0383
MMRC0356
MMRC0282
MMRC0335
MMRC0381
MMRC0421
MMRC0191
MMRC0322
MMRC0191
MMRC0191
MMRC0412
MMRC0392
MMRC0359
MMRC0244
MMRC0406
MMRC0308
MMRC0412
MMRC0383
MMRC0392
MMRC0216
MMRC0375
MMRC0389
MMRC0412
MMRC0406
MMRC0329
MMRC0309
MMRC0338
MMRC0389
MMRC0338
MMRC0412
MMRC0389
MMRC0329
MMRC0286
MMRC0347
MMRC0387
MMRC0412
MMRC0191
MMRC0389
MMRC0343
MMRC0173
MMRC0335
MMRC0286
MMRC0383
MMRC0425
MMRC0412
Previously
treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
doi:10.1038/nature09837
Gene
TFAP2D
TFPI
TG
TGFBR2
THRB
THSD7B
TIMP2
TINAG
TJP3
TLE4
TLL1
TLN2
TLR4
TLR8
TMC5
TMCC1
TMCO6
TMED6
TMEM132B
TMEM150A
TMEM19
TMEM195
TMEM38A
TMEM63B
TMEM63B
TMPRSS11B
TMPRSS13
TMX3
TNC
TNFRSF1A
TNKS1BP1
TNNI3K
TNNI3K
TNPO1
TNPO2
TNPO2
TNRC6B
TNS4
TOPBP1
TOPBP1
TOPBP1
TOX3
TP53
TP53
TP53
TP53AIP1
TRABD
TRAF3
TRAF3
TRAFD1
TRAM1L1
TRAPPC10
TRAPPC10
TRAPPC5
TRIM10
TRIM17
TRIM29
TRIM47
TRIM6
TRIO
TRPM3
TSC1
TSHR
TSHZ2
TSHZ2
TSHZ3
TSHZ3
TSPO2
TTC21A
TTC21B
Chr
6
2
8
3
3
2
17
6
19
9
4
15
9
X
16
3
5
16
12
2
12
7
3
6
6
4
11
18
9
12
11
1
1
5
19
19
22
17
3
3
3
16
17
17
17
11
22
14
14
12
4
21
21
19
6
1
11
17
11
5
9
9
14
20
20
19
19
6
3
2
Position
(strand)
50791110
188069997
133990689(-)
30661282
24163230
138137602
74365323
54296777(+)
3684871
81392014(+)
167144015
60729590
119515407
12847393
19359529
130853105
140003570
67934963
99791634(-)
85680611
70366801
15437260
195841914(+)
44229895
44210804
68776271
117294552
64495382
116888162
6310138
56837122
74623325(+)
74623456(-)
72182866
12685276(+)
12686754
38991755
35906149
134847794(+)
134847856(-)
134858357
51041857
7517839
7518961
7518988
128312908
38702388(+)
102433378
102441819
111074265
118225955
44303484
44332122
7653611
30236494
226669003
119503486
71382742
5588711
14534728
72651243
134770859
80679476
51305306
51305674
36462367
36459529
41118876
39134592
166493767(+)
2nd gene
Chr
Position
(strand)
134015290(+)
19
14493841(-))
14493841(
81481975(-)
12
19
EMR3
124412138(+)
16641397(-)
2
8
122720643(+)
35156775(-)
19
14613995(-)
3
3
22
134851517(+)
134851208(-)
48977497(-)
166524174(-)
Type
Missense
Missense
Tandem duplication
Missense
Nonsense
Missense
Missense
Translocation
Missense
Deletion
Nonsense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Long range
Missense
Missense
Splice site
Translocation
Missense
Missense
Nonsense
Missense
Missense
Missense
Missense
Missense
Translocation
Translocation
Missense
Long range
Splice site
Missense
Missense
Inversion
Inversion
Missense
Missense
Missense
Missense
Nonsense
Nonsense
Long range
Missense
Missense
Missense
Missense
Nonsense
Missense
Missense
Missense
Missense
Missense
Missense
Splice site
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Splice site
Missense
Deletion
AA change
A121V
D59N
V70G
R158*
Q1517H
G114E
P299A
R219*
L51P
S394C
G105R
P223Q
T510S
C314R
F191L
Q51K
I25S
E137_splice
N740D
A78T
R402*
Q78R
G378A
D557H
G209D
G539V
Y49H
Y258_splice
W525C
A19P
G133A
P166T
C275S
Y205D
R196*
E6*
E283fs
D551V
N519K
S15G
A251T
L885*
A158T
T41P
V132L
S301N
G445E
V372I
D2155_splice
L183F
T643A
T441P
F634L
L757Q
S58G
R1004W
G58 splice
G58_splice
D249N
Sample
MMRC0421
MMRC0322
MMRC0387
MMRC0408
MMRC0335
MMRC0392
MMRC0286
MMRC0191
MMRC0329
MMRC0356
MMRC0359
MMRC0335
MMRC0308
MMRC0308
MMRC0344
MMRC0347
MMRC0381
MMRC0412
MMRC0335
MMRC0343
MMRC0421
MMRC0390
MMRC0343
MMRC0242
MMRC0387
MMRC0359
MMRC0423
MMRC0282
MMRC0335
MMRC0427
MMRC0173
MMRC0309
MMRC0309
MMRC0375
MMRC0344
MMRC0191
MMRC0383
MMRC0387
MMRC0376
MMRC0376
MMRC0191
MMRC0376
MMRC0335
MMRC0343
MMRC0347
MMRC0308
MMRC0421
MMRC0309
MMRC0173
MMRC0322
MMRC0173
MMRC0387
MMRC0329
MMRC0329
MMRC0412
MMRC0338
MMRC0408
MMRC0329
MMRC0319
MMRC0344
MMRC0286
MMRC0383
MMRC0344
MMRC0244
MMRC0427
MMRC0344
MMRC0421
MMRC0322
MMRC0381
MMRC0332
Previously
treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Treated
doi:10.1038/nature09837
Gene
TTF1
TTLL6
TTN
TTN
TTN
TUBAL3
TUFT1
TUSC3
TUSC3
TXK
TXNDC5
TXNRD1
TYK2
UBA2
UBASH3A
UBASH3A
UBASH3A
UBASH3A
UBE2G1
UBE2K
UBE3A
UBN1
UBN2
UBTD2
UBTF
UGGT1
UMOD
UMODL1
UNC5B
UNC5C
UNC5D
UNC5D
UPF1
UPP1
USH2A
USP10
USP19
USP22
USP26
USP32
USP34
USP6
USP7
USP9X
UTP20
UVRAG
VAT1L
VAV3
VCAN
VCAN
VDAC3
VEPH1
VGLL3
VIM
VPS13D
VPS13D
VPS45
VPS45
VSIG1
VWA2
VWA2
WDR1
WDR25
WDR5
WDR54
WDR59
WDR66
WDR7
WDR74
WHSC1
Chr
9
17
2
2
2
10
1
8
8
4
6
12
19
19
21
21
17
17
17
4
15
16
7
1
17
2
16
21
10
4
8
2
19
7
1
16
3
17
X
17
2
17
16
X
12
11
16
1
5
5
8
3
3
10
1
1
1
1
X
10
10
4
14
9
2
16
12
18
11
4
Position
(strand)
134267207
44202102
179178424
179224655
179190751
5432910
149813382
15650266
15666088
47773181
7841537(-)
103173371(-)
10338202
39651878
42321723(+)
42444576(-)
7969619(-)
14645553(+)
4145739(+)
39415510
23152179
4850931
138619193
148783772(-)
39603224(-)
128612876
20265062
42404245
72728987
96594518(+)
35658077(+)
122721177(-)
18832645
48113195
213890739
83370008
49127775
20865096
131988659
55615523
61303929
5012036
8916653
40945333
100262507
75396263
76467830
107945904(+)
82853306
82853255
42382102
158581637
87100694
17315685
12255030(+)
12255177(-)
148315338(-)
148307193(-)
107206989
116039167
116035876
9725369(+)
99917161
135996944
74504525
73477148
120890395
52575176
62357109
1835231(+)
2nd gene
Chr
Position
(strand)
MPHOSPH9
20
12
17758553(-)
122265505(+)
METTL2A
21
21
21
21
17
5
17
OLFML2A
IDO2
9
8
8
HCN2
PACS2
2
2
19
14
42733664(+)
42734587(-)
42733404(-)
42734883(+)
57876474(+)
171603083(+)
39647441(-)
126610291(-)
39919674(-)
35672344(+)
107954405(-)
236016644(+)
236016671(-)
559235(-)
104856122(-)
9732688(-)
1872509(-)
Type
Missense
Missense
Missense
Missense
Nonsense
Missense
Missense
Missense
Nonsense
Missense
Translocation
Long range
Missense
Missense
Inversion
Inversion
Translocation
Translocation
Long range
Missense
Missense
Missense
Missense
Translocation
Inversion
Missense
Missense
Missense
Missense
Translocation
Long range
Translocation
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Deletion
Missense
Missense
Missense
Splice site
Missense
Missense
Translocation
Translocation
Translocation
Translocation
Missense
Missense
Missense
Deletion
Missense
Missense
Missense
Missense
Missense
Nonsense
Missense
Deletion
AA change
S275T
M799I
P9075L
E10715V
IE6984>M*
K48N
R203W
V317L
L345*
M411I
E174K
R612K
P47S
L673I
D313N
S1001F
A567P
V357F
G615D
E929K
A771T
F213V
A4721S
Y739C
N535Y
L114V
Q419P
R1303Q
L2534F
T1041N
D346A
K1560N
G1485R
R317C
G262V
T1142R
R1125H
H273Y
R376_splice
V225M
E240K
A296T
S684F
P396S
D49E
S106L
P148T
C865S
G903D
S785*
S785
A350V
Sample
MMRC0332
MMRC0286
MMRC0356
MMRC0376
MMRC0335
MMRC0421
MMRC0425
MMRC0381
MMRC0408
MMRC0319
MMRC0406
MMRC0335
MMRC0319
MMRC0308
MMRC0392
MMRC0392
MMRC0392
MMRC0392
MMRC0376
MMRC0286
MMRC0332
MMRC0392
MMRC0286
MMRC0392
MMRC0319
MMRC0389
MMRC0421
MMRC0282
MMRC0286
MMRC0191
MMRC0309
MMRC0309
MMRC0425
MMRC0347
MMRC0347
MMRC0406
MMRC0319
MMRC0389
MMRC0389
MMRC0359
MMRC0389
MMRC0389
MMRC0392
MMRC0344
MMRC0308
MMRC0004
MMRC0242
MMRC0332
MMRC0381
MMRC0387
MMRC0338
MMRC0332
MMRC0389
MMRC0421
MMRC0389
MMRC0389
MMRC0383
MMRC0383
MMRC0216
MMRC0191
MMRC0359
MMRC0191
MMRC0421
MMRC0319
MMRC0308
MMRC0335
MMRC0381
MMRC0392
MMRC0242
MMRC0421
Previously
treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Untreated
Untreated
Untreated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
doi:10.1038/nature09837
Gene
WHSC1
WHSC1
WHSC1
WHSC1
WHSC1L1
WHSC1L1
WHSC2
WHSC2
XBP1
XBP1
XPO4
ZAN
ZBTB16
ZBTB3
ZBTB33
ZBTB33
ZBTB33
ZBTB45
ZC3H11A
ZC3H14
ZC3H15
ZC3H18
ZC3H18
ZCCHC5
ZCWPW2
ZFP36L1
ZFPM2
ZFYVE1
ZKSCAN3
ZKSCAN5
ZMYM4
ZNF148
ZNF193
ZNF319
ZNF329
ZNF416
ZNF417
ZNF423
ZNF430
ZNF431
ZNF431
ZNF462
ZNF483
ZNF484
ZNF492
ZNF492
ZNF527
ZNF530
ZNF559
ZNF569
ZNF595
ZNF630
ZNF646
ZNF667
ZNF700
ZNF749
ZNF761
ZNF804A
ZNF83
ZNF830
ZNF878
ZNRF3
ZP1
ZP3
ZRANB3
ZSCAN4
ZSWIM7
ZZEF1
ZZEF1
ZZEF1
Chr
4
4
4
4
8
8
4
4
22
22
13
7
2
11
23
23
X
19
1
14
2
16
16
X
3
14
8
14
6
7
1
3
6
16
19
19
19
16
19
19
19
9
9
9
19
19
19
19
19
19
4
X
16
19
19
19
19
2
19
17
19
22
11
7
2
19
17
17
17
17
Position
(strand)
1946876
1889733
1873834(+)
1885576(-)
38276217
38276213
1966247(-)
1966507(+)
27521317
27522135
20294410
100185303(+)
30876558(+)
62276356
119271466(-)
119272900(+)
119272483
63719702
111118279(+)
88110943
187078496
87192225
87171190
77799925
28484449(-)
68327402(+)
106883425
72512119
28441507
98961878
35643226
126434489
28308679
56588088
63331980
62775520
63115314
48229288
21007307(+)
21122980(+)
21123381(-)
108728245
113344664
94649470
22639285
22639569
42571695
62809897
9314103
42595854
45633(+)
47803595
30999336
61645539
11920239
62647400
58644701
185509380
57808751
30313793
12015828
27776888
60398998
75907862
135824102
62881934
15835324(-)
3901057
3864229
3858960
2nd gene
Chr
Position
(strand)
14
14
105247118(+)
105397012(-)
6
6
11
11
102426910(-)
113611495(+)
23
23
119729737(-)
119715889(+)
3
14
19
19
19
DSCAM
DSCAM
14321056(-)
14321021(+)
21
21
202075934(+)
28577758(-)
105397362(-)
33223164(-)
22703537(+)
23120617(-)
40865053(+)
40354174(-)
Type
Missense
Missense
Translocation
Translocation
Missense
Missense
Translocation
Translocation
Missense
Missense
Missense
Translocation
Translocation
Missense
Inversion
Inversion
Missense
Missense
Long range
Missense
Missense
Missense
Missense
Inversion
Long range
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Nonsense
Missense
Missense
Missense
Long range
Long range
Long range
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Translocation
Missense
Missense
Missense
AA change
C1191F
A332D
Y887C
K888N
P326R
L167I
E287K
R503C
I395M
P384L
E339K
Q264R
A276fs
S53T
E217K
S647P
M152V
Q361H
E427K
I1182V
S591A
Y310C
H528R
E235*
Y522N
C30Y
E426Q
P744L
R543Q
G474R
T325N
P420T
Y302N
Q398E
E326K
H516Y
Q394K
Q1397R
T213A
V134F
E358Q
P47L
E338K
E293V
W365C
S510C
A807P
S530N
H302R
R171S
R384Q
H1877P
D2773H
T2924N
Sample
MMRC0282
MMRC0332
MMRC0376
MMRC0319
MMRC0332
MMRC0309
MMRC0332
MMRC0332
MMRC0191
MMRC0383
MMRC0191
MMRC0191
MMRC0191
MMRC0191
MMRC0392
MMRC0392
MMRC0173
MMRC0381
MMRC0332
MMRC0389
MMRC0242
MMRC0347
MMRC0216
MMRC0390
MMRC0421
MMRC0309
MMRC0242
MMRC0322
MMRC0286
MMRC0389
MMRC0406
MMRC0344
MMRC0406
MMRC0359
MMRC0319
MMRC0383
MMRC0389
MMRC0375
MMRC0376
MMRC0421
MMRC0421
MMRC0408
MMRC0344
MMRC0376
MMRC0412
MMRC0423
MMRC0347
MMRC0329
MMRC0389
MMRC0389
MMRC0392
MMRC0375
MMRC0421
MMRC0242
MMRC0344
MMRC0286
MMRC0309
MMRC0389
MMRC0383
MMRC0308
MMRC0389
MMRC0191
MMRC0425
MMRC0191
MMRC0242
MMRC0322
MMRC0392
MMRC0332
MMRC0389
MMRC0412
Previously
treated
Treated
Treated
Untreated
Untreated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Untreated
Treated
Untreated
Treated
Untreated
Untreated
Untreated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Treated
Untreated
Untreated
Treated
Treated
Treated
Treated
Treated
Untreated
Treated
Treated
Untreated
Treated
Treated
Treated
Treated
doi:10.1038/nature09837
Sample
Chromosome
Position
Wild-type Mutated
allele
allele
Gene
Mutation
type
Residue
change
MMRC0338
MMRC0383
MMRC0319
MMRC0282
MMRC0335
MMRC0344
MMRC0322
MMRC0308
MMRC0322
MMRC0335
MMRC0339
MMRC0347
MMRC0375
MMRC0335
MMRC0343
MMRC0347
MMRC0335
MMRC0308
MMRC0004
MMRC0216
MMRC0282
MMRC0335
MMRC0308
MMRC0329
MMRC0319
MMRC0308
MMRC0343
MMRC0376
MMRC0359
MMRC0191
MMRC0319
MMRC0284
MMRC0309
MMRC0356
MMRC0375
MMRC0338
MMRC0322
MMRC0004
MMRC0423
MMRC0329
MMRC0173
MMRC0028
MMRC0322
MMRC0383
MMRC0284
MMRC0216
MMRC0344
MMRC0322
MMRC0338
MMRC0028
8
11
3
2
5
17
14
7
11
11
16
16
5
8
8
1
1
8
12
12
9
9
9
12
13
13
13
1
6
1
17
19
3
4
17
14
7
3
7
11
12
10
10
10
10
1
1
1
5
21
39644716
129780757
127356171
231835342
159982131
38510440
92830943
81480722
69165273
69165400
67421112
74120718
79066681
3244433
2810771
33931142
33962836
114100564
110213632
110256876
89507784
89486233
89511987
47520116
72234065
72244372
72244028
153308070
94025844
94774262
77630632
44213752
48391853
155726959
7286827
64580830
4763284
71109797
113998137
65567324
48785727
25901622
87474414
87618868
87363311
220782114
114310366
87330920
132431102
40059472
G
C
G
A
C
C
C
G
A
A
C
G
A
C
T
C
G
G
G
G
C
G
A
C
C
T
A
G
C
T
C
A
G
C
T
C
G
G
T
G
T
T
C
C
C
G
C
C
T
G
ADAM18
ADAMTS8
ALDH1L1
ARMC9
ATP10B
BRCA1
BTBD7
CACNA2D1
CCND1
CCND1
CDH1
CHST5
CMYA5
CSMD1
CSMD1
CSMD2
CSMD2
CSMD3
CUX2
CUX2
DAPK1
DAPK1
DAPK1
DDX23
DIS3
DIS3
DIS3
EFNA4
EPHA7
F3
FASN
FBXO27
FBXW12
FGA
FGF11
FNTB
FOXK1
FOXP1
FOXP2
GAL3ST3
GPD1
GPR158
GRID1
GRID1
GRID1
HHIPL2
HIPK1
HS2ST1
HSPA4
IGSF5
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Mi
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Mi
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Mi
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Mi
Missense
Missense
Splice site
Missense
Missense
Missense
Missense
Nonsense
Missense
Missense
p.E457K
p.C859Y
p.N212K
p.Y369F
p V554I
p.V554I
p.C91F
p.R59K
p.I421M
p.Q4R
p.K46N
p.R784C
p.R356C
p.I2113V
p.V766I
V766I
p.S3073C
p.E1303K
p.R878C
p.P313L
p.R110H
p.V1059I
p.H964Q
p.G699E
p.K1394R
K1394R
p.D121N
p.R750K
p.S447R
p.V474G
p.R196H
p.A625T
p.T87S
p.A2430T
p.V138G
V138G
p.E98Q
p.G358R
p.L200H
p.R291C
p.R395Q
p.P407L
p.S100T
p.P176A
p.S117A
S117A
p.I518T
A
T
T
T
T
A
T
C
G
T
T
A
G
T
A
T
A
A
A
A
A
A
G
T
T
G
C
A
T
A
T
C
C
T
A
T
A
A
A
C
G
C
A
A
A
C
T
T
G
A
p.R277M
p.D812Y
p.I327M
p.T777I
p.R190*
p.L87R
p.V81I
Genotyping result
True positive
True positive
True positive
False positive
Tr e positive
True
positi e
True positive
True positive
False positive
True positive
True positive
True positive
Assay failed
True positive
T
True
positive
iti
True positive
True positive
True positive
True positive
True positive
True positive
True positive
True positive
T
True
positive
iti
True positive
True positive
True positive
True positive
True positive
True positive
True positive
True positive
F l positive
False
iti
True positive
True positive
True positive
True positive
True positive
True positive
True positive
Assay failed
T
True
positive
iti
True positive
False positive
True positive
True positive
True positive
True positive
True positive
True positive
True positive
Supplementary Table 4 Validation of point mutations. Genotyping was performed

using a mass spectrometry-based method (Sequenom).
doi:10.1038/nature09837
Sample
Chromosome
Position
Wild-type
allele
Mutated
allele
Gene
Mutation
type
Residue
change
MMRC0423
MMRC0339
MMRC0028
MMRC0339
MMRC0423
MMRC0308
MMRC0344
MMRC0347
MMRC0173
MMRC0173
MMRC0375
MMRC0335
MMRC0344
MMRC0376
MMRC0173
MMRC0319
MMRC0319
MMRC0308
MMRC0309
MMRC0191
MMRC0356
MMRC0309
MMRC0216
MMRC0329
MMRC0329
MMRC0322
MMRC0343
MMRC0282
MMRC0347
MMRC0282
MMRC0282
MMRC0216
MMRC0284
MMRC0375
MMRC0173
MMRC0356
MMRC0356
MMRC0359
MMRC0335
MMRC0191
MMRC0376
MMRC0335
MMRC0335
MMRC0356
MMRC0319
MMRC0004
MMRC0359
MMRC0191
MMRC0383
MMRC0173
6
6
16
5
1
8
12
12
X
7
1
22
22
2
2
10
4
4
5
5
1
2
5
10
4
2
3
X
X
20
20
7
3
3
2
11
16
4
15
19
2
2
2
2
3
11
10
10
19
17
339972
339972
53522742
52254425
150041224
23235653
25134396
1813952
43400553
100626060
43576423
24730698
24577473
152092285
152289034
21160467
149254800
149400600
37387135
37353901
245818830
178934702
140235327
119124316
129031759
135636644
197714230
153281344
153281355
34989013
34989043
83430493
166233893
166208477
74303586
130278478
2752059
167144015
60729590
12686754
179224655
179190751
179190752
179178424
49127775
75396263
116035876
116039167
62775520
3954844
A
A
C
A
G
C
G
G
C
C
C
T
G
G
C
C
C
A
T
G
C
G
G
C
A
T
A
A
A
C
C
C
G
T
G
C
C
C
T
C
T
C
A
G
T
C
C
C
A
T
G
G
T
C
A
G
C
A
T
T
A
A
A
A
T
T
T
C
G
A
A
C
T
T
C
A
T
G
C
G
G
A
A
A
A
T
T
T
C
T
A
A
C
A
A
T
T
T
T
G
IRF4
IRF4
IRX5
ITGA1
LINGO4
LOXL2
LRMP
LRTM2
MAOA
MOGAT3
MPL
MYO18B
MYO18B
NEB
NEB
NEBL
NR3C2
NR3C2
NUP155
NUP155
OR2G2
OSBPL6
PCDHA12
PDZD8
PLK4
RAB3GAP1
RNF168
RPL10
RPL10
SAMHD1
SAMHD1
SEMA3A
SI
SI
SLC4A5
SNX19
SRRM2
TLL1
TLN2
TNPO2
TTN
TTN
TTN
TTN
USP19
UVRAG
VWA2
VWA2
ZNF416
ZZEF1
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Nonsense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Mi
Missense
Missense
Missense
Missense
Missense
Missense
Nonsense
Missense
Splice site
Missense
Nonsense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
Missense
p.K123R
p.K123R
p.A44V
p.E785A
p T194I
p.T194I
p.G413R
p.E202Q
p.R306Q
p.A7V
p.E305K
p.T49N
p.I2116N
p.R1271Q
p P5553S
p.P5553S
p.A200T
p.V501M
p.E902K
p.F626C
p.T154P
p.P692S
p.C182*
p.E401Q
p G29V
p.G29V
p.R138H
p.E631D
p.L780Q
p.L71H
p.E66G
p.I70L
p.E228Q
p.D218H
p.W608C
W608C
p.T850I
p.M1395L
p.P1099L
p.E819K
p.S510F
p.R219*
p.L51P
Genotyping result
True positive
True positive
True positive
True positive
Tr e positive
True
positi e
True positive
True positive
True positive
Assay failed
True positive
True positive
True positive
Assay failed
True positive
Assay failed
True positive
True positive
True positive
True positive
True positive
True positive
True positive
True positive
True positive
True positive
True positive
True positive
Assay failed
Assay failed
True positive
True positive
T
True
positive
iti
True positive
Assay failed
True positive
True positive
True positive
True positive
True positive
True positive
p E10715V True positive
p.E10715V
p.E6793*
True positive
p.I6792M
True positive
p.P8883L
True positive
p.N535Y
True positive
p.R317C
True positive
p.P396S
True positive
p.S684F
True positive
p.Y522N
True positive
p T469P
p.T469P
False positive
doi:10.1038/nature09837
Sample
Chromosome
Position
Insertion or
deletion
Inserted/deletedsequence
MMRC0427
9562800
Deletion
TTCAGATACATGATGCCAGGATCACACTCTTCTCC
ADAM17 Truepositive
MMRC0381
56764144
Insertion
ARHGEF3 Truepositive
MMRC0286
52926231
Insertion
C1orf163 Truepositive
MMRC0412
117967150
Deletion
TAAC
MMRC0244
14692207
Deletion
MMRC0381
239674222
Deletion
HDAC4
Falsepositive
MMRC0387
142546379
Deletion
SLITRK4
Truepositive
MMRC0309
21
32933263
Deletion
SYNJ1
Truepositive
MMRC0309
14
102433378
Insertion
TRAF3
Truepositive
MMRC0347
16
87192225
Deletion
ZC3H18
Truepositive
Gene
FAM46C
Genotyping
result
Truepositive
FAM84A Falsepositive
Supplementary Table 5 Validation of small indels. Genotyping was performed using

a mass spectrometry-based method (Sequenom). Only assays that could successfully
be designed are shown.
doi:10.1038/nature09837
Gene
Chr
Position (strand)
EIF3B
LRRK2
Chr
Position (strand)
Type
AA change
Sample
Previously treated
2385341
Missense
Y760F
MMRC0343
Treated
12
38918064
Missense
E155K
MMRC0286
Untreated
LRRK2
12
38994132
Missense
I1543S
MMRC0344
Treated
LRRK2
12
38953506(+)
18
8522903(+)
Translocation
MMRC0376
Untreated
LRRK2
12
38953703(-)
18
8522979(-)
Translocation
MMRC0376
Untreated
RPL10
153281344
Missense
E66G
MMRC0282
Treated
RPS6KA1 1
26754634
Nonsense
Q283*
MMRC0335
Treated
XBP1
22
27521317
Missense
P326R
MMRC0191
Treated
XBP1
22
27522135
Missense
L167I
MMRC0383
Treated
Supplementary Table 6 Mutations in genes involved in protein translation,

stability, and the unfolded protein response. These mutations were not significant on
their own, but are considered in conjunction with the statistically significant DIS3 and
FAM46C mutations.
doi:10.1038/nature09837
Gene
Chr
Position
(strand)
Type
AA change Sample
Likely effect of mutation on gene

Previously treated Effect of gene on NF-B function
BTRC
10
103288069
Missense
A536G
MMRC0286
Untreated
Activation
CARD11
2930442
Missense
Y631H
MMRC0375
Treated
Activation
CARD11
2925677
Missense
D789N
MMRC0425
Untreated
Activation
CYLD
16
49378431(+) 16
MMRC0335
Treated
Inactivation
IKBIP
12
97531523
Missense
E342K
MMRC0319
Untreated
Unknown
IKBKB
42283051
Missense
K171E
MMRC0427
Treated
Activation
MAP3K1
56209516(-) 8
42575852(+) Translocation
MMRC0344
Treated
Activation
MAP3K14
17
40720277(+) 17
40725216(-) Deletion
MMRC0319
Untreated
Activation
RIPK4
21
42034912
Missense
Q504K
MMRC0347
Untreated
Activation
TLR4
119515407
Missense
S394C
MMRC0308
Treated
Activation
TNFRSF1A 12
6310138
Missense
G209D
MMRC0427
Treated
Activation
TRAF3
14
102433378
Insertion (FS) E283fs
MMRC0309
Untreated
Inactivation
Loss (frame-shift)
TRAF3
14
102441819
Missense
MMRC0173
Treated
Inactivation
Loss (high FI mutation affecting MATH,

i.e. NIK-interacting, domain)
Chr
Position
(strand)
49379310(-) Deletion
D551V
Loss (deletion)
Supplementary Table 7 Point mutations and re-arrangements of genes affecting

activation of NF-B. Point mutations achieved significance as part of a gene set (p =
0.016).
doi:10.1038/nature09837
Gene
Chr
Position
(strand)
Type
AA change
Sample
Previously
treated
F3
94774262
Missense
T87S
MMRC0191
Treated
F5
167772526
Missense
D1605N
MMRC0389
Treated
FGA
155726959
Missense
G358R
MMRC0356
Untreated
FGA
155726404
Missense
E543K
MMRC0389
Treated
FGG
155753196
Missense
H6Y
MMRC0376
Untreated
TFPI
188069997
Missense
D59N
MMRC0322
Untreated
Supplementary Table 8 Mutations in genes involved in generation of the fibrin

clot. These mutations achieved significance as part of a gene set in an unbiased search
of the MSigDB (q = 0.0054 after correction for multiple hypothesis testing).
doi:10.1038/nature09837
Chr
Start
End
Length
Muts
Samples
p-value
q-value
88908630
88909380
750
1.55E-06
4.00E-02
88939740
88939930
190
2.21E-11
1.70E-06
1.68E-08
88940090
88940430
340
1.62E-13
88940600
88940670
70
3.41E-06
7.05E-02
88940800
88941190
390
1.85E-14
4.42E-09
4.42E-09
88941490
88941690
200
7.22E-15
88941840
88942340
500
18
1.28E-14
4.42E-09
88946120
88946140
20
1.66E-07
6.57E-03
88946300
88946650
350
4.02E-13
3.83E-08
1.86E-02
89027740
89028620
880
5.70E-07
89276310
89277630
1320
6.89E-12
5.65E-07
89400240
89401200
960
1.87E-05
2.41E-01
188944110
188948430
4320
23
10
1.33E-13
1.43E-08
14
105121160
105122380
1220
6.09E-06
1.13E-01
14
105122930
105129920
6990
1.77E-05
2.34E-01
14
105178690
105186230
7540
11
6.67E-14
8.35E-09
14
105246120
105250860
4740
25
11
2.76E-14
4.42E-09
14
105277850
105285620
7770
10
2.20E-14
4.42E-09
14
105309360
105313440
4080
12
9.33E-15
4.42E-09
14
105394150
105395580
1430
6.55E-15
4.42E-09
14
105395780
105398150
2370
34
14
2.44E-14
4.42E-09
14
105398300
105398980
680
25
13
2 72E 14
2.72E-14
4 42E 09
4.42E-09
14
105399330
105399630
300
1.46E-09
8.70E-05
14
105399840
105403470
3630
102
21
2.70E-14
4.42E-09
14
105420980
105421100
120
1.33E-05
1.87E-01
14
105565150
105565450
300
1.71E-05
2.31E-01
14
105657690
105657780
90
3.19E-06
6.84E-02
14
105861960
105862770
810
2.53E-10
1.72E-05
14
105876070
105876860
790
1.30E-06
3.55E-02
14
106240900
106241490
590
6 00E-13
6.00E
13
5 49E-08
5.49E
08
14
106249830
106250300
470
34
19
2.35E-14
4.42E-09
14
106330320
106330790
470
9.04E-07
2.69E-02
22
21359460
21359930
470
3.00E-09
1.74E-04
22
21376460
21377500
1040
2.38E-12
2.02E-07
22
21528380
21529390
1010
2.94E-14
4.42E-09
22
21553070
21553180
110
1.55E-15
3.70E-09
22
21553290
21553620
330
23
10
7.77E-15
4.42E-09
22
21556900
21558010
1110
2.98E-14
4.42E-09
22
21559860
21560570
710
8.56E-11
6.36E-06
22
21560700
21560820
120
7.64E-10
4.66E-05
22
21561130
21561410
280
1.15E-10
8.26E-06
22
21571780
21573590
1810
2.77E-07
1.02E-02
22
21576990
21579030
2040
3.05E-13
3.02E-08
22
21607620
21608750
1130
3.18E-06
6.84E-02
Supplementary Table 9 Non-coding regulatory potential analysis identifies

multiple sites that exhibit somatic hypermutation. Regions are Ig (chromosome 2),
BCL6 promoter/intron (chromosome 3), IgH (chromosome 14), and Ig (chromosome 22).
doi:10.1038/nature09837
Chr
1
1
1
Position
554731
555225
555269
Gene
AK125248 (IGR)
AK125248 (IGR)
AK125248 (IGR)
Ref
T
G
C
Mut
C
A
T
Sample
MM-0343
MM-0425
MM-0309
Putative binding sites

GATA-1/stress-response element
none
STAT5a
82793242
TTLL7/LPHN2 (IGR)
MM-0375
HOXA3
82793250
TTLL7/LPHN2 (IGR)
MM-0343
deltaEF1
147333845
NBPFA (IGR)
MM-0387
STAT4
147334295
NBPFA (IGR)
MM-0408
paired box factor 2/STAT4/STAT5a
147334296
NBPFA (IGR)
MM-0408
paired box factor 2/STAT4/STAT5a/Dof3
147334380
NBPFA (IGR)
MM-0425
HOXA3/STAT5a
40865609
SLC8A1/PKDCC (IGR)
MM-0387
alcohol dehydrogenase gene regulator 1
40865611
SLC8A1/PKDCC (IGR)
MM-0389
Dof2/Dof3/paired box factor 2/alcohol dehydrogenase gene regulator 1
149273928
ZIC4/AGTR1 (IGR)
MM-0335
CdxA
149274006
ZIC4/AGTR1 (IGR)
MM-0332
engrailed 1
189142836
BCL6/LPP (IGR)
MM-0421
paired box factor 2/Dof3/STAT4/STAT5a
189143134
BCL6/LPP (IGR)
MM-0343
none
189143142
BCL6/LPP (IGR)
MM 0387
MM-0387
STAT1/STAT3/STAT4/STAT5 /STAT6/ i d box

STAT1/STAT3/STAT4/STAT5a/STAT6/paired
b factor
f t 2/Ikaros
2/Ik
2
189143159
BCL6/LPP (IGR)
MM-0242
STAT1/STAT3/STAT4/STAT5a/STAT6
189143285
BCL6/LPP (IGR)
MM-0242
Dof2/Dof3/paired box factor 2
189143311
BCL6/LPP (IGR)
MM-0343
none
189143391
BCL6/LPP (IGR)
MM-0376
none
189143392
BCL6/LPP (IGR)
MM-0376
none
189440883
LPP (Intron)
MM-0335
paired box factor 2/Dof1
189440884
LPP (Intron)
MM-0344
Dof1
189441175
LPP (Intron)
MM-0412
Ikaros 2/GATA-2/GATA-6/RAV1 (AP2 interacting)/deltaEF1
157902239
PDGFC (3'
(3 -UTR)
UTR)
MM 0387
MM-0387
STAT5a/heat shock factor/paired box factor 2/Dof1/Dof3

STAT5a/heat-shock
157903235
PDGFC (3'-UTR)
MM-0408
Hunchback
157903658
PDGFC (3'-UTR)
MM-0309
none
4
4
4
4
4
4
4
4
4
7
7
9
9
9
157904101
39875936
39876045
39876457
62180565
62180776
62181208
7819489
7819515
92754257
92754258
16564622
16564872
16564948
PDGFC (Intron)
RHOH (Intron)
RHOH (Intron)
RHOH (Intron)
LPHN3 (Intron)
LPHN3 (Intron)
LPHN3 (Intron)
AFAP1 (Intron)
AFAP1 (Intron)
CCDC132 (Intron)
CCDC132 (Intron)
BNC2 (Intron)
BNC2 (Intron)
BNC2 (Intron)
T
C
A
A
T
T
T
G
C
T
A
C
C
A
G
T
G
G
G
A
G
A
T
A
T
A
G
G
MM-0191
MM-0191
MM-0387
MM-0387
MM-0389
MM-0390
MM-0425
MM-0242
MM-0309
MM-0343
MM-0387
MM-0412
MM-0335
MM-0412
GATA-1/GATA-1/GATA-6
Ikaros 2/STAT1/STAT3/STAT4/STAT5a/STAT6/GATA-1
GATA-1/GATA-2
heat shock factor/STAT5a
none
paired box 2/Dof3
Deformed/HOXA3/octamer factor 1
none
none
none
none
paired box factor 2/STAT3/STAT4/STAT5a/STAT6
none
paired box factor 2/Dof1/GATA-6
12
120943427
BCL7A (Promoter)
MM-0412
engrailed 1
12
120943444
BCL7A (Promoter)
MM-0390
HOXA3/deltaEF1
12
120943453
BCL7A (Promoter)
MM-0406
deltaEF1/STAT4/GATA-1
12
120943777
BCL7A (Promoter)
MM-0390
cap signal for transcription initiation
12
120945822
BCL7A (Intron)
(I t )
MM 0390
MM-0390
c-Myc/AhR
M /AhR nuclear
l
ttranslocator/USF
l
t /USF
12
120946479
BCL7A (Intron)
MM-0421
paired box factor 2/sex-determining region Y gene product/GATA-1/GATA-2
12
14
14
14
14
17
17
17
17
120946774
68328421
68328818
68328974
68329209
8108665
8110148
8110537
8110620
BCL7A (Intron)
ZFP36L1 (Intron)
ZFP36L1 (Intron)
ZFP36L1 (Intron)
ZFP36L1 (Intron)
PFAS (Intron)
PFAS (Intron)
PFAS (Intron)
PFAS (Intron)
T
A
G
T
C
C
C
C
C
C
G
C
C
G
T
A
G
G
MM-0309
MM-0344
MM-0191
MM-0392
MM-0412
MM-0356
MM-0392
MM-0392
MM-0392
STAT5a/heat shock factor/HOXA3

CCAAT-enhancer binding factor/Ultrabithoraz
STAT5a/heat shock factor
none
paired box factor 2
none
alcohol dehydrogenase gene regulator 1
Meis1
GATA-2
20
20
60329271
60329391
LAMA5 (Synonymous)
LAMA5 (Intron)
G
G
A
C
MM-0447
MM-0356
STAT4
STAT5a
Supplementary Table 10 Potential transcription factor binding sites targeted by

mutations in significantly mutated regulatory regions. Binding sites were predicted
using the publicly-available version of the TRANSFAC database (ref.).
doi:10.1038/nature09837
Amplicon
Primer sequence (sense)
Primer sequence (antisense)
Annealing
temperature (oC)
chr1:554202-555412
TCG TTT GAA ATG GTC ATC CA
TGC GTA GTT GGG TTT GGT TT
55
chr1:82793145-82793343
TGT TAC AAT GGC TGT GCT AAA
AAA GGC CAA TCA TGA TGA GAA
55
chr3:149273859-149274108
chr3:149273859
149274108
TGA AGC TAC AAA AGC TCT AAG AAA A
TGC AAA ATA GGC CAA CAA CA
55
chr3:189142479-189143663
CGC TCA GAG AGA TCA ATG GAC
TGT GTG TGG TGA GTA GGA AAG G
55
chr3:189440767-189441356
GCT TAC AGC TTG CCT AAC AAG G
TTT AAT ATA GCC AAT AGG GAG GTT C
55
chr4:7819353-7819601
AGC AGA GCC ACA GTT TCC AT
TCT GAC GTA TTC CGG ATG TG
55
chr4:62180499-62181471
AGG AAA TGA GTT TTT CGT TTT G
TGC TCC AAT AGT CAG CTC CA
55
chr4:157901940-157902946
CCA CCT ATC ACC AAG CAT TTC
TGT TGG CTT TTC TAA TCT TGT TAA A
55
chr4:157902805-157903743
chr4:157902805
157903743
TCA TCT TTG TTC CTC TGG CTA
GAG CAC CAT GAG GAG TGT GA
55
chr9:16564308-16565147
CAT GCA AAA AGA CAG GTG TGA
CTG TTC TGT CAT CTG TGA AAT GTG
55
chr12:120942955-120943524
CCC GGC CAG TAT TTG TTC T
GCC CCC AGA AGT TCT CTT GT
55
chr20:60328896-60329577
CCT GCA CTG ACA CAT GTA CG
GTG CTG GCC CTA CCT TCT C
55
Supplementary Table 11 Primer sequences and annealing temperatures for PCR

of RP regions. All reactions comprised 35 cycles of PCR.
doi:10.1038/nature09837
Gene
OSS
Permutation
score
TSPY6P
6291.512653
0.018
LOC283352
5226 686439
5226.686439
HOXA9
3217.111381
0.012
PTPRZ1
2705.699055
F2R
2321.240087
0.006
KIAA0125
2315.404911
COL4A6
2260.239257
0.006
FSTL5
1650.941992
0.012
POPDC3
1611.195061
0.036
NRN1
1266.903751
ELMOD1
1219.562329
0.008
TRPM3
1108.72542
0.01
TMPRSS11E
1106.40036
0.016
SAMD3
1032.63057
0.01
GABRR1
873.944921
0.008
SYNPO2
820 740759
820.740759
0 008
0.008
PRSS21
788.115356
0.01
GBA3
763.936377
HES1
754.020388
0.044
GNG11
750.429829
Supplementary Table 12 Top 20 outliers by OSS analysis. Only genes with a

permutation score less than 0.05 are shown.
doi:10.1038/nature09837
Gene
Annealing
temperature (oC)
F3
CCA AAC CCG TCA ATC AAG TC
TGT ATA AAT TAA GTC CTT GCC AAA AA
54.5
TFPI
TGA AAG TCT GGA AGA GTG CAA A
GCT GGA GTG AGA CAC CAT GA
54.5
FGA
CAT CAA TCT GCC TGC AAA GA
TCT GCA GAA GCT GGA TAT GCT
53 5
53.5
FGG
TGC TAC CAG AGA CAA CTG CTG
TTC AAA GTA GCA GCG TCT ATC A
53
LDHA
GAC CTA CGT GGC TTG GAA GA
AAT CTC CAT GTT CCC CAA GG
53
Supplementary Table 13 Primer sequences and annealing temperatures for RTPCR of coagulation factors. All reactions comprised 35 cycles of PCR.
doi:10.1038/nature09837
Amplicon
Annealing
temperature (oC)
DIS3 RNB
CCTCTTCTGGCTGATTCTTGA
TGCAGGAAAAAGAAATGTGG
55
DIS3 RNB
CAAAAGCCGATGAACAATGA
GCCGAATCTCCTACTTTTCCA
56
FAM46C
TTGAGTCCTCATGGCAACAC
CGTACATGCTCTCCCCAATC
56
FAM46C
TGAAGGACATCGTCCAGACC
AGACACACGGTGCTCTCGTT
56
FAM46C
TGAAGGAGGCATATGTGCAG
TTTCCAACGTGGCACTGTAA
56
FAM46C
CCCACAGACCAGGAAGAAAT
CAGCACAACTTTCATGTAACTGC
56
Supplementary Table 14 Primer sequences and annealing temperatures for PCR

of DIS3 (RNB domain) and FAM46C. All reactions comprised 35 cycles of PCR.
doi:10.1038/nature09837
Cell line
DNA change
Protein change
Del 13q21 at other allele?
H929
c.G1570C
p.A524P
Yes
INA6
None
JIM3
None
KMS11
None
KMS12-BM
None
KMS12-PE
None
L363
None
MM.1S
None
OCI-My5
None
OCI-My7
None
OPM2
None
RPMI8226
None
SKMM1
c.A2533G
p.I845V
Yes
U266
None
XG6
None
Supplementary Table 15 DIS3 RNB domain mutations in cell lines. PCR and
Sanger sequencing was used to detect mutations in the cell lines shown.
doi:10.1038/nature09837
Cell line
DNA change
Protein change
Del 1p12 at other allele?
H929
c.278_279insC
p.L93fsX15
Yes
INA6
None
JIM3
None
p M270V
p.M270V
Yes
p.E178A
Yes
p.I173fsX36
No
KMS11
None
KMS12-BM None
KMS12-PE None
L363
None
LP1
Hom. del. exon 1*
MM 1S
MM.1S
c A808G
c.A808G
OCI-My1
None
OCI-My5
None
OCI-My7
None
OPM2
c.A533C
RPMI8226 None
SKMM1
c.519delT
U266
None
XG6
None
*Determined by aCGH
Supplementary Table 16 FAM46C mutations in cell lines. PCR and Sanger

sequencing was used to detect mutations in 16 of the cell lines shown. In addition, aCGH
profiles of cell lines were examined for larger re-arrangements and the homozygous
deletion in LP1 was identified (FAM46C expression is zero in this cell line).

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SUPPLEMENTARY INFORMATION

Patients with MM (n=38)

WGS libraries (n=23)

Exome hybrid capture (n=16)

WGS libraries (n=23)

Exome hybrid capture (n=16)

RESEARCH SUPPLEMENTARY INFORMATION

67% (all exons)

88% (targeted exons)

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

MMRC dataset samples (n = 304)

Cell line samples (n = 52)

Arkansas dataset samples (n = 414)

Relative HOXA9 expression

Supplementary Figure 4 Patterns of HOXA9 expression in MM

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

Example: definition of regions in

Obtain genome-wide regulatory

Smooth RP scores by averaging in a

Generate discrete regions of

2.38 x 106 RP regions genome-wide

For a given region:

Total good quality coverage of region

Use binomial test to calculate

RESEARCH SUPPLEMENTARY INFORMATION

Supplementary Figure 10 Copy-number profiles showing tumor-in-normal contamination in two

RESEARCH SUPPLEMENTARY INFORMATION

Not in bait set

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

LODT > log10 ( 0.5 10 6 ) 6.3 whichguaranteesthatourfalsepositiverate,duetonoise

sites,werequire LODN > log10 0.5 10 2 2.3 sincenondbSNPgermlinevariantsoccur

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

RESEARCH SUPPLEMENTARY INFORMATION

del 13q14; del 17p13

del 13q14; del 1p32

*Spiked CCND1 expression absent, despite t(11;14)