TUBB3locvps
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TableS1:Detailedclinico-pathologicalinformationforthePUMsAbbreviations:PM=primarymanagement,LBD=largestbasaldiameter,UH=ultrasoundheight,CBI=ciliarybodyinvolvement,EOE=extraocularextension,HPF=highpowerfields,Enuc=enucleation,PBT=protonbeamRXT,LR=localresection,N=no,Y=yes,N/A=notassessed,del=deletion,amp=amplification,M3=monosomy3*=fromaSNPdataSampleIDPUMtoMUM01PUM02(MUM03)PUMtoMUM05PUM04(MUM07)PUM05(MUM08)PUMtoMUM09PUMtoMUM10PUM08(MUM11)PUMtoMUM13PUMtoMUM17PUMtoMUM18PUM18(MUM21)AgeatPM645439696448666560675467GenderMaleMaleFemaleFemaleFemaleMaleMaleFemaleFemaleMaleMaleMaleTypeofPMEnucEnucEnucEnucEnucPBTEnucLR,EnucEnucPBTPBTEnucLBD(mm)15.
516.
618.
718.
918.
78.
716.
514.
3418.
516.
215.
2UH(mm)7.
52.
48.
389.
72.
237.
64.
33.
99.
414.
1CBINNNYNNNNYNNNEOENNNNNNNNY(Episclera)NNNEpithelioidCellsYYYYYYYYYYNRYClosedLoopsYYYYNNRYYNNRNRYMitoticCount(40HPF)516286NR10204NRNR52Chr.
3status*N/AHeterozygousdeletionsandROHN/AHeterozygousdeletionsandROHHeterozygousdeletionsandROHN/AN/AHeterozygousdeletionsandROHN/AN/AN/AHeterozygousdeletionsandROHChr.
8qstatus*N/APartialampN/AAmpAmpN/AN/AAmpN/AN/AN/AAmpTableS2:Detailedclinico-pathologicalinformationfortheMUMsAbbreviations:dia=diameter,NR=notreported,N=no,Y=yes,NA=notapplicable,del=deletion,amp=amplification,D3=disomy3,M3=monosomy3,MM=metastaticmelanoma*=fromaSNPdata**=timebetweenprimarydiagnosisandlastfollow-upSampleIDMUM01MUM03MUM05MUM07MUM08MUM09MUM10MUM11MUM13MUM17MUM18MUM21TypeofSampleLiverresectionLiverresectionLiverresectionLiverresectionLiverresectionLiverresectionLiverresectionLaparoscopicbiopsyLaparoscopicbiopsyLiverresectionLiverresectionLiverresectionLesionsize(mm)40x35x1316x15x1415x11x1037x36x6225x20x320india11x9x104india12india5x2x135x25x23NRLiverSegmentIVaVIII,IIIVIII,V,VIINRVIINANANRV,VINRCellTypeMixedMixedMixedMixedEpithelioidEpithelioidSpindleSpindleMixedMixedSpindleNRPigmentationNYYYYNNRNYYYNRChr.
3status*HeterozygousdeletionsandROHHeterozygousdeletionsandROHHeterozygousdeletionsandROHIsodisomyHeterozygousdeletionsandROHIsodisomyIsodisomyHeterozygousdeletionsandROHM3M3D3M3Chr.
8qstatus*AmpPartialampAmpAmpAmpAmpAmpAmpAmpAmpAmpAmpDeceasedYNYYYYYYYYNYCauseofDeathMM---MMMMMMMMMMMMMMMM---MMOverallSurvivalTime(years)5.
513.
4**4.
22.
72.
94.
43.
31.
98.
11.
211.
1**4.
3TableS3:Listof193geneswithCNVsidentifiedinPUM02,PUM04,PUM05,andPUM08GeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolAARSCENPTDUS2KLHDC4MBTPS1NUTF2SLC7A6TUBB3ACDCHMP1AEDC4KLHL36MC1ROSGIN1SLC7A6OSURAHPACSF3CHTF8ENKD1LCATMIR140PABPN1LSMG1P7USP10ADAD2CIRH1AESRP2LINC00304MIR1538PARD6ASNAI3VAC14AFG3L1PCLEC18AEXOSC6LINC00311MIR1972-1PDFSNAI3-AS1VILLAGRPCLEC18CFAM157CLOC100129697MIR1972-2PDPRSNORD111VPS4AANKRD11COG4FAM65ALOC100131303MIR26A1PDXDC2PSNORD111BVPS9D1APRTCOG8FAM92BLOC100287036MIR3155APFKFB3SNORD68VPS9D1-AS1ASB13COTL1FANCALOC100289580MIR3155BPIEZO1SNTB2WFDC1ATP2C2CPNE7FBXO31LOC100505942MIR4722PLA2G15SPATA2LWWP2ATP6V0D1CRISPLD2FUKLOC100506083MIR5093PLCD1SPATA33ZC3H18BANPCTCFGALNSLOC101927817MIR5189PRDM7SPG7ZCCHC14C16orf86CTRLGAS8LOC101928682MIR6773PRMT7SPIRE2ZDHHC1C16orf95CTU2GAS8-AS1LOC101928708MIR6775PSKH1ST3GAL2ZDHHC7CA5ACYB5BGFOD2LOC101928737MLYCDPSMB10TAF1CZFPM1CALML3CYBAHAS3LOC101928880MTSS1LRANBP10TANGO6ZNF276CALML3-AS1DBNDD1HSD11B2LOC102724467MVDRBM17TCF25ZNF469CALML5DDX19AHSDL1LOC339059NECAB2RLTPRTERF2ZNF778CBFA2T3DDX19BIL15RALOC399715NET1RNF166THAP11TableS4:Listof135geneswithCNVsidentifiedinallPUM-MUMpairsGeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolADAM6CYP11B2HGH1LYPD2MIR6849PUF60TMED10P1ZNF7ADCK5DENND3HSF1MAF1MIR6850PYCRLTMEM249ZNF707AGO2DGAT1JRKMAFAMIR6893RECQL4TONSLARCEEF1DKIAA0125MAFA-AS1MIR7112RHPN1TOP1MTARHGAP39EPPK1KIAA1875MAPK15MIR7641-2RHPN1-AS1TRAPPC9BAI1ETV5KIFC2MFSD3MIR937RNF5P1TSNARE1BOP1EXOSC4LINC00051MIR1268AMIR939RNU6-2TSTA3BREA2FAM83HLINC01300MIR1302-7MROH1RPL8VPS28C8orf31FAM83H-AS1LOC100133669MIR4472-1MROH5SCRIBZC3H3C8orf33FBXL6LOC100287098MIR4507MROH6SCRT1ZFP41C8orf82FOXH1LOC100288181MIR4537NAPRTSCXZNF16CCDC166GLI4LOC100507316MIR4538NRBP2SHARPINZNF250CDC42P3GMLLRRC14MIR4539OPLAHSLC39A4ZNF251CHRAC1GPAA1LRRC24MIR4664PARP10SLC45A4ZNF252PCOMMD5GPIHBP1LY6DMIR661PLECSLC52A2ZNF252P-AS1CPSF1GPR20LY6EMIR6845PPP1R16ASLURP1ZNF34CYC1GPTLY6HMIR6846PSCASPATC1ZNF517CYHR1GRINALY6KMIR6847PTK2THEM6ZNF623CYP11B1GSDMDLYNX1MIR6848PTP4A3TIGD5ZNF696TableS5:DetailedresultsofSNPanalysisandIHCforallMUMsassessedSampleGeneMUM01MUM05MUM07MUM08MUM10MUM11MUM17MUM18MUM21C-MYCCNamplificationamplificationamplificationamplificationamplificationamplificationamplificationamplificationamplificationAsCNampwAIampwAIampwAIampwAIampwAIampwAIampwAIampw/oAIampwAIIHC(nuclear)moderate50%moderate70%weak5%strong80%weak20%strong95%moderate40%moderate90%strong80%IHC(score)452727467BAP1CNunchangeddeletionunchangedunchangedunchangeddeletiondeletionunchangeddeletionAsCNAllelichomozygosityLOHAllelichomozygosityAllelichomozygosityAllelichomozygosityLOHLOHunchangedLOHIHC(nuclear)negativenegativenegativenegativenegativenegativenegativepositivenegativeAbbreviations:CN=copy-numberanalysis,AsCN=allele-specificcopy-numberanalysis,IHC=immunohistochemistry,amp=amplification,LOH=lossofheterozygosity,AI=allelicimbalanceFigureS1:OverviewofchromosomaldistributionofgeneCNVsinMUMs.
Top:Amplificationswerefoundonallidentifiedchromosomes,exceptforchr.
3.
Themostcommongeneamplificationsoccurredonchr.
8,followedbychr.
20,17,and19.
Manyamplifiedgeneswereseenin50%(6/12)orlesssampleswithinthecohort.
Bottom:Deletionswerelessfrequentandmainlyoccurredonchr.
3.
However,notmorethan8/12MUMsshowedthesamegenedeletion.
FigureS2:ComparisonofCNandAsCNanlysis.
OntheleftthechromosomaldistributionfortheCNVsidentifiedwithintheMUMsaredepictedforchr.
3.
OntherightthechromosomaldistributionfortheidentifiedAsCNwithinthecohortareshownforchr.
3.
MostlyregionswithnoamplificationordeletionbyCNanalysisshowregionsofhomozygosity(ROH)inAsCNanalysis.
.
FigureS3:VennDiagrams(VD)ofdetailedanalysisofthefivePUM-MUMpairs.
TheindividualVDsforeachpair(atthetopandbottom)revealinformationregardingthecountofalteredgenesbeinguniquetoMUM(green),uniquetoPUM(red),andaresharedbetweenbothpartnersofthepair(yellow,intersect).
VDscombiningthisinformation(middle)revealthatfortheMUMsnoCNVwassharedbymorethanthreesamples,135geneswerefoundinallfivepairs,and194CNVsweredetectedinfourPUMs.
516.
618.
718.
918.
78.
716.
514.
3418.
516.
215.
2UH(mm)7.
52.
48.
389.
72.
237.
64.
33.
99.
414.
1CBINNNYNNNNYNNNEOENNNNNNNNY(Episclera)NNNEpithelioidCellsYYYYYYYYYYNRYClosedLoopsYYYYNNRYYNNRNRYMitoticCount(40HPF)516286NR10204NRNR52Chr.
3status*N/AHeterozygousdeletionsandROHN/AHeterozygousdeletionsandROHHeterozygousdeletionsandROHN/AN/AHeterozygousdeletionsandROHN/AN/AN/AHeterozygousdeletionsandROHChr.
8qstatus*N/APartialampN/AAmpAmpN/AN/AAmpN/AN/AN/AAmpTableS2:Detailedclinico-pathologicalinformationfortheMUMsAbbreviations:dia=diameter,NR=notreported,N=no,Y=yes,NA=notapplicable,del=deletion,amp=amplification,D3=disomy3,M3=monosomy3,MM=metastaticmelanoma*=fromaSNPdata**=timebetweenprimarydiagnosisandlastfollow-upSampleIDMUM01MUM03MUM05MUM07MUM08MUM09MUM10MUM11MUM13MUM17MUM18MUM21TypeofSampleLiverresectionLiverresectionLiverresectionLiverresectionLiverresectionLiverresectionLiverresectionLaparoscopicbiopsyLaparoscopicbiopsyLiverresectionLiverresectionLiverresectionLesionsize(mm)40x35x1316x15x1415x11x1037x36x6225x20x320india11x9x104india12india5x2x135x25x23NRLiverSegmentIVaVIII,IIIVIII,V,VIINRVIINANANRV,VINRCellTypeMixedMixedMixedMixedEpithelioidEpithelioidSpindleSpindleMixedMixedSpindleNRPigmentationNYYYYNNRNYYYNRChr.
3status*HeterozygousdeletionsandROHHeterozygousdeletionsandROHHeterozygousdeletionsandROHIsodisomyHeterozygousdeletionsandROHIsodisomyIsodisomyHeterozygousdeletionsandROHM3M3D3M3Chr.
8qstatus*AmpPartialampAmpAmpAmpAmpAmpAmpAmpAmpAmpAmpDeceasedYNYYYYYYYYNYCauseofDeathMM---MMMMMMMMMMMMMMMM---MMOverallSurvivalTime(years)5.
513.
4**4.
22.
72.
94.
43.
31.
98.
11.
211.
1**4.
3TableS3:Listof193geneswithCNVsidentifiedinPUM02,PUM04,PUM05,andPUM08GeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolAARSCENPTDUS2KLHDC4MBTPS1NUTF2SLC7A6TUBB3ACDCHMP1AEDC4KLHL36MC1ROSGIN1SLC7A6OSURAHPACSF3CHTF8ENKD1LCATMIR140PABPN1LSMG1P7USP10ADAD2CIRH1AESRP2LINC00304MIR1538PARD6ASNAI3VAC14AFG3L1PCLEC18AEXOSC6LINC00311MIR1972-1PDFSNAI3-AS1VILLAGRPCLEC18CFAM157CLOC100129697MIR1972-2PDPRSNORD111VPS4AANKRD11COG4FAM65ALOC100131303MIR26A1PDXDC2PSNORD111BVPS9D1APRTCOG8FAM92BLOC100287036MIR3155APFKFB3SNORD68VPS9D1-AS1ASB13COTL1FANCALOC100289580MIR3155BPIEZO1SNTB2WFDC1ATP2C2CPNE7FBXO31LOC100505942MIR4722PLA2G15SPATA2LWWP2ATP6V0D1CRISPLD2FUKLOC100506083MIR5093PLCD1SPATA33ZC3H18BANPCTCFGALNSLOC101927817MIR5189PRDM7SPG7ZCCHC14C16orf86CTRLGAS8LOC101928682MIR6773PRMT7SPIRE2ZDHHC1C16orf95CTU2GAS8-AS1LOC101928708MIR6775PSKH1ST3GAL2ZDHHC7CA5ACYB5BGFOD2LOC101928737MLYCDPSMB10TAF1CZFPM1CALML3CYBAHAS3LOC101928880MTSS1LRANBP10TANGO6ZNF276CALML3-AS1DBNDD1HSD11B2LOC102724467MVDRBM17TCF25ZNF469CALML5DDX19AHSDL1LOC339059NECAB2RLTPRTERF2ZNF778CBFA2T3DDX19BIL15RALOC399715NET1RNF166THAP11TableS4:Listof135geneswithCNVsidentifiedinallPUM-MUMpairsGeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolGeneSymbolADAM6CYP11B2HGH1LYPD2MIR6849PUF60TMED10P1ZNF7ADCK5DENND3HSF1MAF1MIR6850PYCRLTMEM249ZNF707AGO2DGAT1JRKMAFAMIR6893RECQL4TONSLARCEEF1DKIAA0125MAFA-AS1MIR7112RHPN1TOP1MTARHGAP39EPPK1KIAA1875MAPK15MIR7641-2RHPN1-AS1TRAPPC9BAI1ETV5KIFC2MFSD3MIR937RNF5P1TSNARE1BOP1EXOSC4LINC00051MIR1268AMIR939RNU6-2TSTA3BREA2FAM83HLINC01300MIR1302-7MROH1RPL8VPS28C8orf31FAM83H-AS1LOC100133669MIR4472-1MROH5SCRIBZC3H3C8orf33FBXL6LOC100287098MIR4507MROH6SCRT1ZFP41C8orf82FOXH1LOC100288181MIR4537NAPRTSCXZNF16CCDC166GLI4LOC100507316MIR4538NRBP2SHARPINZNF250CDC42P3GMLLRRC14MIR4539OPLAHSLC39A4ZNF251CHRAC1GPAA1LRRC24MIR4664PARP10SLC45A4ZNF252PCOMMD5GPIHBP1LY6DMIR661PLECSLC52A2ZNF252P-AS1CPSF1GPR20LY6EMIR6845PPP1R16ASLURP1ZNF34CYC1GPTLY6HMIR6846PSCASPATC1ZNF517CYHR1GRINALY6KMIR6847PTK2THEM6ZNF623CYP11B1GSDMDLYNX1MIR6848PTP4A3TIGD5ZNF696TableS5:DetailedresultsofSNPanalysisandIHCforallMUMsassessedSampleGeneMUM01MUM05MUM07MUM08MUM10MUM11MUM17MUM18MUM21C-MYCCNamplificationamplificationamplificationamplificationamplificationamplificationamplificationamplificationamplificationAsCNampwAIampwAIampwAIampwAIampwAIampwAIampwAIampw/oAIampwAIIHC(nuclear)moderate50%moderate70%weak5%strong80%weak20%strong95%moderate40%moderate90%strong80%IHC(score)452727467BAP1CNunchangeddeletionunchangedunchangedunchangeddeletiondeletionunchangeddeletionAsCNAllelichomozygosityLOHAllelichomozygosityAllelichomozygosityAllelichomozygosityLOHLOHunchangedLOHIHC(nuclear)negativenegativenegativenegativenegativenegativenegativepositivenegativeAbbreviations:CN=copy-numberanalysis,AsCN=allele-specificcopy-numberanalysis,IHC=immunohistochemistry,amp=amplification,LOH=lossofheterozygosity,AI=allelicimbalanceFigureS1:OverviewofchromosomaldistributionofgeneCNVsinMUMs.
Top:Amplificationswerefoundonallidentifiedchromosomes,exceptforchr.
3.
Themostcommongeneamplificationsoccurredonchr.
8,followedbychr.
20,17,and19.
Manyamplifiedgeneswereseenin50%(6/12)orlesssampleswithinthecohort.
Bottom:Deletionswerelessfrequentandmainlyoccurredonchr.
3.
However,notmorethan8/12MUMsshowedthesamegenedeletion.
FigureS2:ComparisonofCNandAsCNanlysis.
OntheleftthechromosomaldistributionfortheCNVsidentifiedwithintheMUMsaredepictedforchr.
3.
OntherightthechromosomaldistributionfortheidentifiedAsCNwithinthecohortareshownforchr.
3.
MostlyregionswithnoamplificationordeletionbyCNanalysisshowregionsofhomozygosity(ROH)inAsCNanalysis.
.
FigureS3:VennDiagrams(VD)ofdetailedanalysisofthefivePUM-MUMpairs.
TheindividualVDsforeachpair(atthetopandbottom)revealinformationregardingthecountofalteredgenesbeinguniquetoMUM(green),uniquetoPUM(red),andaresharedbetweenbothpartnersofthepair(yellow,intersect).
VDscombiningthisinformation(middle)revealthatfortheMUMsnoCNVwassharedbymorethanthreesamples,135geneswerefoundinallfivepairs,and194CNVsweredetectedinfourPUMs.
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