Supplementary Figures

Fig. S1. Distribution of total mutation pool. a) Statistics of different mutational types. b) The distribution of mutational allele frequency. c) Circle graph illustrating the chromosomal assignment of total mutation pool. The outer ring provides an overview of detected ctDNA mutations in each chromosome, while the inner ring shows the mutation burden of each chromosome.

Fig. S2. DNMT3A mutations in the experimental cohort. The upper graph shows all 19 DNMT3A mutations and their protein localization. The red rectangle indicates DNA_methylase domains. The lollipop graph is generated by online tools of cbioportal (http://www.cbioportal.org/visualize). The lower graph illustrates the diagnostic age distribution for patients with and without DNMT3A mutations. The p value is calculated by nonparametric t-test.

Fig. S3. Overview of clinical actionability for patients with drug-sensitive and resistant mutations.

Each horizontal column represents an individual patients. Columns with different colors indicate diverse actionable mutations, and the length of column represents the number of mutations. Patients are divided into three groups using horizontal dotted lines, according to the mutation types.

Fig. S4. Concordance and mutant allele frequencies for matched sample pairs. Venn diagrams present the mutation overlap between matched tissue and blood samples. Scatter diagrams show the correlation between the allele frequencies of overlapping mutations in ctDNA vs. tissue DNA. Each dot represents an overlapping mutation, and horizontal/vertical axis indicates its normalized MAF in

4 ctDNA/tissue DNA. The red dashed lines indicate the cut-off value (25%) for clonal and subclonal mutations.

Supplementary Tables

Table S1. Sequencing panel used in targeted capture hybridization

Genes with all exons captured (170 genes, 2,735 exons) ABL1 CDK4 FGFR4 MDM4 PSMB1 ABL2 CDK6 FLCN MED12 PSMB5 AKT1 CDK8 FLT1 MET PTCH1 AKT2 CDKN1A FLT3 MITF PTCH2 AKT3 CDKN1B FLT4 MLH1 PTEN ALK CDKN2A FOXA1 MLH3 PTPN11 APC CDKN2B FOXL2 MPL RAF1 AR CHEK1 GAB2 MS4A1 RARA ARAF CHEK2 GATA3 MSH2 RB1 ATM CRKL GNA11 MSH3 RET ATR CSF1R GNAQ MSH6 RHEB AURKA CTNNB1 GNAS MTOR RHOA AURKB DDR1 HDAC1 MYC RICTOR AXL DDR2 HDAC4 MYD88 RNF43 BAP1 DNMT3A HGF NF1 ROCK1 BCL2 EGFR HRAS NF2 ROS1 BRAF EPHA2 IDH1 NOTCH1 RPS6KB1 BRCA1 EPHA3 IDH2 NOTCH2 SMARCA4 BRCA2 EPHA5 IGF1R NOTCH3 SMARCB1 BRD2 ERBB2 IL7R NOTCH4 SMO BRD3 ERBB3 INPP4B NRAS SRC BRD4 ERBB4 IRS2 NTRK1 STAT1 BTK ERCC1 JAK1 NTRK3 STAT3 C11orf30 ERG JAK2 PALB2 STK11 C1QA ESR1 JAK3 PDGFRA SYK C1S EZH2 KDR PDGFRB TMPRSS2 CBL FAT 1 KIT PDK1 TOP1 CCND1 FBXW7 KRAS PIK3CA TP53 CCND2 FCGR2A MAP2K1 PIK3CB TSC1 CCND3 FCGR2B MAP2K2 PIK3R1 TSC2 CCNE1 FCGR3A MAPK1 PIK3R2 VEGFA CD274 FGFR1 MAPK3 PMS1 VHL CDH1 FGFR2 MCL1 PMS2 XPO1 CDK13 FGFR3 MDM2 PRKAA1 XRCC1 Genes with partial exons captured (847 genes, 1,122 exons) ABCA10 ABCA8 ABCB7 ABCC8 ABCF2 ACE ACER2 ACOT11 ACPP ACSL1 ACSM5 ACSS3 ACTL6B ADAM23 ADAM33 ADAMTS12 ADAMTS16 ADAMTS19 ADAMTS20 ADAMTS5 ADAMTSL1 ADD2 AGMAT AGTPBP1 AHCTF1 AK5 AKR1B10 AKR1C1 ALDH1A3 ALDH2 ALG5 ALX4 AMOT ANK2 ANKRD13D ANKRD20A4 ANKRD27 ANKRD28 ANKRD30A ANKRD30B ANKRD36B ANO2 AP1B1 AP1G2 AP3B1 APAF1 APLP2 APMAP APPL2 AQP12A ARFGAP1 ARFRP1 ARHGAP35 ARHGAP40 ARHGEF1 ARHGEF7 ARNTL ARPC4-TTLL3 ASH2L ASTN1 ASXL2 ATAD2B ATG9B ATP10B ATP10D ATP12A ATP2C1 ATP6V0A2 ATP8B2 ATXN2

ATXN7L2 BAX BBS9 BCAS1 BCAS2 BLOC1S1 BMPR1B BRF1 BRSK2 BRWD3 BSG BTNL3 BTRC C12orf5 C19orf38 C1orf112 C1orf35 C20orf112 C2orf47 C2orf62 C7orf53 C9orf114 C9orf43 CACNA1A CACNA1D CACNA1E CADM2 CAMKK1 CAPRIN1 CARS CARS2 CASC4 CASP8 CASP8AP2 CASQ2 CATSPER2 CBFB CBX4 CCDC155 CCDC159 CCDC17 CCT3 CCT6B CD1E CD300LF CD5L CD9 CD97 CD99 CDH18 CDH24 CDH26 CDK11A CDK12 CDK14 CDK18 CDK19 CDS1 CEACAM20 CECR2 CELA2B CGN CHD3 CHD4 CHD6 CHI3L1 CISD3 CLCN7 CLEC16A CLINT1 CNGB3 CNKSR2 CNOT3 CNOT4 CNTN1 CNTN4 CNTN5 CNTNAP3B CNTNAP5 COASY COL14A1 COL16A1 COL19A1 COL1A1 COL25A1 COL4A5 COL4A6 COL5A1 COL5A2 COL5A3 COL6A5 COL6A6 COL9A1 C OPA COPG1 C PA1 CPSF3 CPSF6 CRTAM CRTAP CRYBG3 CSMD1 CSMD3 CSN3 CSNK1E CSPP1 CTCF CTIF CTNNA2 CTSF CYP2A13 CYP3A4 CYP4A11 CYTH4 DCLK2 DCST1 DDB1 DDX24 DDX3X DEPDC4 DGKK DHCR24 DHDDS DHX9 DIAPH1 DKC1 DLST DMD DMXL1 DMXL2 DNAH10 DNAH5 DNAH9 DNAJC11 DNAJC9 DNTTIP1 DOCK11 DOCK3 DOT1L DPP10 DPP4 DRGX DUOX1 DYSF DZANK1 ECHDC1 EDN1 EEF1A1 EFCAB5 EFCAB6 EFCAB7 EFHA2 EFNA5 EIF1AX EIF2B5 EIF2C2 EIF3E EIF3I EIF4ENIF1 EIF4H ELAVL3 ELL3 EMID2 ENPP2 ENTPD6 EPB41L2 EPB41L4B EPHB1 EPS8L3 ESD ETNK2 ETV6 EXOC4 EXOC5 EXOC6 EXOC7 EXTL3 EYA4 F8 F9 FAH FAM114A2 FAM131B FAM135B FAM13C FAM157B FAM177B FAM21A FAM 3 A FAM49A FAM49B FAM 5 C FAM86B1 FAN 1 FANCC FAS T K FAT E1 FBN2 FDCSP FLNC FLOT2 FLT3LG FMN2 FMNL3 FNDC4 FNIP2 FOLH1 FOXJ2 FRG1 FRG2B FRMD4A FRMPD2 FRMPD4 FSD2 FSHR FUBP1 FUNDC1 GAB3 GABRD GAD2 GALNT13 GALNT14 GFRAL GIGYF1 GINS4 GIPR GKN2 GLB1L3 GLYR1 GMDS GNPTAB GOLGA4 GPAT2 GPATCH2 GPR114 GPR125 GPR133 GPR144 GPS2 GRIA3 GRIK2 GUCY1A3 GUCY2C GYLTL1B HAAO HAP1 HAUS5 HAUS6 HCN1 HDAC6 HEATR7B2 HECTD4 HECW1 HECW2 HID1 HIST1H3B HLA-DRB1 HLA-DRB5 HMCN1 HMHA1 HNF4A HOMER2 HPS3 HPS4 HSPA12B HSPD1 HYDIN IBSP IFT172 IGSF9

IKBKAP IKBKE IL11RA IL13RA2 IL1RAPL1 IL27RA IMPG1 INHBA INPP5J IQCA1 ITFG2 ITGA8 ITGA9 ITIH1 ITLN2 ITM2A ITPKB ITPR1 KCNAB2 KCNH6 KCNQ2 KDM4A KDM6A KEAP1 KIAA0195 KIAA0226 KIAA0319 KIAA0922 KIAA1191 KIAA1199 KIAA1211L KIF13A KIF1B KIF26B KIFAP3 KIFC1 KIR2DL3 KIR3DL3 KLHL1 KLHL14 KLK1 KMT2B KMT2C KRT2 KRT9 KRTAP5-5 KTN1 L3MBTL1 LARP1 LCN10 LCT LCTL LETM1 LGALS13 LILRB3 LILRB4 LIPN LMAN1L LMBR1L LPCAT4 LPHN3 LRBA LRP1B LRP2 LRP4 LRRC16B LRRC2 LRRC7 LRRC72 LRRD1 LRRFIP2 LRSAM1 LTBP1 LUC7L2 LUZP4 MAEL MAGI1 MAN2A1 MAP2 MAP2K4 MAP3K1 MAP4K1 MAPKAPK3 MAPRE3 MAST1 MBIP MBTPS2 MCF2L2 MCOLN2 MDGA2 MDN1 MED23 MEFV METTL14 METTL5 MGAM MICALL1 MID1 MIER2 MLL MLPH MORC1 MORN1 MRPL1 MRPL24 MRPS18B MSI1 MTA2 MTM1 MTR MTTP MUC5B MUS81 MYB MYBPC2 MYCBP2 MYH15 MYH2 MYH4 MYH8 MYH9 MYL5 MYL6 MYLK2 MYO3A MYOM1 NACAD NARF NAT10 NAV3 NBPF1 NBPF10 NCF2 NCKAP1 NCOR1 NCOR2 NEK5 NELL1 NFE2L2 NIPBL NLGN3 NLRC3 NLRP4 NMI NOP2 NOS1 NOS2 NRXN1 NRXN2 NT5C3L NTM NUDCD2 NUP205 NUP210 NUTM1 NWD1 NXF1 NXF5 OBP2A OBP2B OCA2 ODZ3 OR2T4 OR4A15 OR4C6 OR5L2 OR6F1 OSBPL10 OTOA OTOGL OVCH1 P4HB PABPC4 PAC S 2 PAE P PAGE1 PARK2 PARP4 PCK2 PCLO PCNT PCNXL2 PCSK5 PCYT1A PDCD6 PDE1C PDE2A PDE4DIP PDIA5 PDILT PDRG1 PEX6 PGAP1 PHACTR3 PHF20L1 PHYH PI4KB PIP4K2C PIP5K1C PIWIL1 PKD1L2 PKHD1 PKLR PLAC8 PLCB4 PLCZ1 PLEC PLK2 PLOD3 PLXNA1 POLDIP2 POLE POLR2J POLR3B POLR3GL POLRMT POM121L12 POTEG PPA1 PPDPF PPEF1 PPFIBP2 PPIL2 PPP1R17 PPP4R4 PQBP1 PREB PREX2 PRKACA PRKAG3 PRKCD PRKDC PRKX PRRX1 PRSS1 PRUNE PSG2 PSG5 PSIP1 PSMC4 PSMC6 PSTPIP1 PTBP3 PTCD3 PTGES3L-AARSD1 PTGS2 PTPLAD1 PTPN13 PTPRA PTPRD PTPRM PYHIN1 QRICH2 RAB1B RAB3GAP2 RAB6A RAC2 RALBP1 RAPGEF2 RARB RASEF RBM6 RBMX RCC1 REC8 REG1B RELN RERE RFWD2 RFX3

RNF215 RNF219 RPL22 RPL36A RPS5 RPS6KA1 RPTOR RPUSD4 RREB1 RRP7A RUNDC3A RUNX1 RYR2 RYR3 SAFB2 SAG SAGE1 SAMD8 SCN10A SCN3A SCN7A SCN9A SDK2 SEC14L4 SEC24B SEH1L SELP SEMA6A SEPT12. SERPINA7 SETD1B SETD2 SF1 SF3B1 SF3B14 SF3B3 SGCZ SGIP1 SGK1 SGPL1 SH2D3A SH3BGR SH3PXD2A SHISA4 SI SIDT2 SIK3 SIM1 SIM2 SLC13A3 SLC17A6 SLC17A8 SLC25A1 SLC25A30 SLC26A3 SLC2A2 SLC30A5 SLC35B2 SLC35B4 SLC38A4 SLC38A5 SLC43A1 SLC45A1 SLC4A10 SLC4A4 SLC5A1 SLC6A5 SLC8A1 SLCO1B7 SLCO5A1 SMTN SNTG1 SORCS3 SPAG16 SPATA13 SPG20 SPINT1 SPPL2A SPPL3 SPRED1 SPTA1 SRRT SSBP3 SSH2 SSPO ST18 ST6GALNAC1 STAG2 STAT4 STAT6 STK11IP STK31 STX3 SULT1A4 SUPT5H SUPT6H SYCP2L SYNE1 SYNE2 SYNJ2 TAF1B TAF6 TARBP1 TBC1D1 TBC1D21 TBC1D3 TBC1D5 TBL1X TBP TBX15 TBX22 TBX3 TCF20 TCF4 TCP10 TCP11 TEK TESC TEX35 TFDP1 TGDS TGM2 TGM5 THBS2 THEM5 THOC1 THSD7A THSD7B TIMD4 TIMM44 TIMP3 TJP3 TLE1 TLL1 TMC2 TMED8 TMEM104 TMEM120B TMEM132D TMEM145 TMEM247 TMEM80 TMEM87A TMTC4 TMX3 TNFAIP6 TNFSF4 TNN TNNT1 TNR TNS3 TP53BP1 TPCN1 TPH2 TPMT TPTE TRIM33 TRIM51 TRIM58 TRIML1 TRIO TRIP11 TRMT112 TRPC5 TRUB1 TSGA10 TSKS TSPAN12 TSR2 TTF2 TTN TUBA3C TUBGCP4 TUBGCP5 TYK2 TYRP1 U2AF1 U2AF2 UBASH3A UBE2Q1 UBE4B UCHL3 UCK2 UGT8 ULK3 UMOD UNC13A UNC13D UNC5D USP12 USP34 USP39 USP45 USP48 VAV1 VEZF1 VILL VIT VPS13A VPS33B VSIG4 WAS WASL WDR44 WDR52 WDR62 WDR66 WDR72 WDTC1 WLS WSCD2 WWP2 XBP1 XPO4 XPO5 ZAP70 ZBTB8OS ZC3H13 ZC3H7B ZDHHC11 ZFC3H1 ZFR ZMYM4 ZNF143 ZNF350 ZNF385A ZNF414 ZNF512B ZNF541 ZNF563 ZNF614 ZNF687 ZNF705B ZNF705G ZNF711 ZNF804B ZSWIM8

Table S2. Targeted mutations identified from patient blood samples

Patient Gene pHGVS M (%) Genomic location P001 KRAS p.G12R 53.68 12:25398284-25398285 P001 TP53 p.C238Y 34.39 17:7577567-7577568 P001 SF3B1 p.K700E 25.55 2:198266833-198266834 P001 CDH23 p.Y2254N 0.20 10:73556907-73556908 P002 FBXW7 NA 37.50 4:153271191-153271192 P002 KRAS p.G13D 20.70 12:25398280-25398281 P002 EGFR p.E114K 20.60 7:55211096-55211097 P002 KRAS p.M72V 10.50 12:25380243-25380244 P002 ESR1 p.K266T 8.20 6:152265343-152265344 P002 APC p.P1319Lfs*2 6.70 5:112175246-112175247 P002 FGFR2 p.K668R 4.20 10:123246921-123246922 P002 EPHA3 p.V73G 3.80 3:89259073-89259074 P002 AR p.F814C 0.60 X:66941796-66941797 P002 IL7R p.L406P 0.60 5:35876424-35876425 P002 ABL1 p.K727T 0.30 9:133759856-133759857 P002 BAP1 p.H94Q 0.30 3:52442066-52442067 P003 ACIN1 p.S649* 13.46 14:23548771-23548772 P003 TP53 p.R248Q 11.95 17:7577537-7577538 P003 FLT4 p.N299K 8.24 5:180056346-180056347 P003 IGF1R p.M1041R 2.73 15:99478217-99478218 P003 OR4C6 p.V197G 0.95 11:55433231-55433232 P003 MAPK1 p.L115H 0.85 22:22160286-22160287 P003 RET p.Y146* 0.72 10:43597889-43597890 P004 DNMT3A p.Y546S 1.55 2:25463288-25463289 P004 APC p.K1308* 1.37 5:112175212-112175213 P004 KRAS p.G12D 1.27 12:25398283-25398284 P004 BRD3 p.E709K 0.83 9:136898767-136898768 P004 BAP1 p.V478M 0.50 3:52437728-52437729 P005 PALB2 p.G793V 0.50 16:23641096-23641097 P005 NOTCH4 p.L605H 0.40 6:32184768-32184769 P006 CTNNB1 p.T41A 0.86 3:41266123-41266124 P006 ALK p.R1212H 0.76 2:29443581-29443582 P006 NTRK3 p.G633E 0.75 15:88472656-88472657 P006 TSC2 p.V1618I 0.59 16:2136734-2136735 P007 PTCH2 p.Q317R 11.10 1:45295418-45295419 P007 NOTCH1 p.K538E 8.30 9:139410489-139410490 P007 APC p.C447* 8.10 5:112157620-112157621 P007 HECW1 p.Q197R 8.10 7:43436446-43436447 P007 POM121L12 p.A28T 8.10 7:53103445-53103446 P007 EPHA3 p.K653E 7.80 3:89468422-89468423 P007 NOTCH3 p.A399P 7.80 19:15299982-15299983 P007 POM121L12 p.W53C 7.80 7:53103522-53103523 P007 FBXW7 p.G359V 7.70 4:153247371-153247372 P007 SMARCA4 p.K687E 7.40 19:11118634-11118635 P007 IRS2 p.E636D 7.30 13:110436492-110436493 P007 IL7R p.N182I 7.20 5:35873588-35873589 P007 KRAS p.G12D 7.20 12:25398283-25398284 P007 SMARCA4 p.R89H 7.10 19:11095991-11095992 P007 ERBB3 p.L1009V 7.00 12:56493708-56493709 P007 NOTCH3 p.L949P 7.00 19:15291919-15291920 P007 ABCC11 p.A746S 6.00 16:48231959-48231960

P007 AKT2 p.W11* 5.40 19:40771141-40771142 P007 PIK3CA p.E545K 5.20 3:178936090-178936091 P007 RET p.E480K 3.10 10:43606828-43606829 P007 BRCA2 p.G2168* 2.00 13:32914993-32914994 P007 MLL3 p.Q1993* 1.20 7:151878967-151878968 P007 NOTCH3 p.A2223V 1.00 19:15271770-15271771 P007 IRS2 p.R558P 0.90 13:110436727-110436728 P007 NOTCH3 p.R1837H 0.90 19:15276754-15276755 P007 BRCA1 p.P871L 0.80 17:41244935-41244936 P007 BRCA1 p.E1038G 0.80 17:41244434-41244435 P007 NOTCH3 p.Y1021* 0.80 19:15291570-15291571 P007 NOTCH4 p.P204L 0.80 6:32188942-32188943 P007 PMS2 p.T485K 0.80 7:6026941-6026942 P007 RNF43 p.L418M 0.80 17:56435884-56435885 P007 BRCA1 p.K1183R 0.60 17:41243999-41244000 P007 BRCA1 p.S1613G 0.60 17:41223093-41223094 P007 JAK3 p.G160C 0.60 19:17953923-17953924 P007 RNF43 p.A365T 0.60 17:56436043-56436044 P008 TP53 p.C275Y 67.60 17:7577113-7577114 P008 KRAS p.G13D 67.30 12:25398280-25398281 P008 TMPRSS2 p.V197M 0.60 21:42852496-42852497 P009 KRAS p.G12V 2.26 12:25398283-25398284 P009 TP53 p.R248Q 2.15 17:7577537-7577538 P009 APC p.S1389Ffs*6 1.67 5:112175454-112175454 P010 TP53 NA 81.90 17:7579590-7579591 P010 KRAS p.G12V 38.70 12:25398283-25398284 P010 BAP1 p.R666Kfs*26 2.50 3:52436676-52436677 P010 MAP3K1 p.A5G 0.40 5:56111413-56111414 P010 EZH2 p.N376Y 0.20 7:148515082-148515083 P011 TP53 p.G244V 62.00 17:7577549-7577550 P011 CCNE1 p.D63V 21.69 19:30308050-30308051 P011 DCST1 p.R433H 0.74 1:155018625-155018626 P011 ERBB2 p.V665M 0.54 17:37879617-37879618 P012 SETD1B p.H8Tfs*27 2.76 12:122242657-122242658 P012 C20orf112 p.Y133Tfs*20 1.72 20:31041555-31041556 P012 GATA3 p.P135Rfs*60 1.16 10:8100424-8100425 P012 MAP2K2 p.A19T 1.08 19:4123817-4123818 P012 NOTCH2 p.D773V 1.03 1:120496212-120496213 P012 PTCH1 p.R1308Efs*64 0.92 9:98209616-98209617 P012 PDGFRB p.V823I 0.90 5:149500569-149500570 P012 ERG p.Y424Tfs*12 0.88 21:39755516-39755517 P012 OSBPL10 p.A200E 0.78 3:31871661-31871662 P012 PALB2 p.A245V 0.74 16:23647132-23647133 P012 CHEK2 p.A94V 0.66 22:29130428-29130429 P012 PTPRD p.T1428I 0.62 9:8389334-8389335 P012 PCK2 p.I450M 0.58 14:24572076-24572077 P012 PIK3CA p.G1049S 0.57 3:178952089-178952090 P012 SMARCA4 p.V698I 0.57 19:11118667-11118668 P012 NOTCH2 p.T1132M 0.55 1:120480031-120480032 P012 PTEN p.K267Rfs*9 0.54 10:89717769-89717770 P012 KRAS p.A146T 0.50 12:25378561-25378562 P012 TARBP1 p.W1173C 0.50 1:234556483-234556484 P012 CTNNB1 p.T41A 0.49 3:41266123-41266124 P012 PTCH1 p.G1296Dfs*76 0.46 9:98209652-98209653

P012 FGFR3 p.G382R 0.44 4:1806118-1806119 P012 CDKN2A p.H83Y 0.14 9:21971110-21971111 P013 RAF1 p.S257L 14.80 3:12645698-12645699 P013 TP53 p.R175H 11.80 17:7578405-7578406 P013 APC p.E1494Kfs*13 10.87 5:112175769-112175770 P013 ERBB4 p.A4V 7.06 2:213403243-213403244 P013 APC p.E911Ifs*7 4.16 5:112174021-112174023 P013 FGFR2 p.H720L 0.69 10:123244944-123244945 P013 BRD2 p.I542K 0.68 6:32945948-32945949 P013 UNC13A p.R495L 0.66 19:17760351-17760352 P013 NF2 p.S267R 0.58 22:30057318-30057319 P013 PDGFRB p.T347S 0.53 5:149512400-149512401 P014 TP53 NA 61.07 17:7578175-7578176 P014 ALK p.G452W 40.09 2:29551275-29551276 P014 APC p.R283* 39.57 5:112151203-112151204 P014 KRAS p.G12V 36.94 12:25398283-25398284 P014 BCL2L11 NA 26.32 2:111907618-111907619 P014 MITF p.A264T 22.10 3:70008502-70008503 P014 APC p.L1488Yfs*19 18.58 5:112175751-112175752 P014 TMEM132D p.G407R 2.69 12:129822258-129822259 P014 PIK3CA p.E545K 1.12 3:178936090-178936091 P015 BBS9 p.A455T 25.64 7:33388712-33388713 P015 EPHA5 p.A672T 15.95 4:66231685-66231686 P016 IGF1R p.F777L 3.19 15:99465505-99465506 P016 ESR1 p.V392I 3.16 6:152332867-152332868 P016 TP53 p.Y163C 2.52 17:7578441-7578442 P016 APC p.R499* 1.75 5:112162890-112162891 P016 KRAS p.G13D 1.69 12:25398280-25398281 P016 SETD2 p.K547* 0.87 3:47164486-47164487 P017 NOTCH3 p.V1183M 1.97 19:15290006-15290007 P018 GLYR1 p.N395Y 1.15 16:4862185-4862186 P018 BRCA1 p.P1190H 0.80 17:41243978-41243979 P018 KRAS p.A146T 0.77 12:25378561-25378562 P018 APC p.K1085* 0.75 5:112174543-112174544 P018 PIK3CA p.E545K 0.54 3:178936090-178936091 P018 KRAS p.T50Nfs*37 0.34 12:25380309-25380309 P019 KRAS p.G12D 7.86 12:25398283-25398284 P019 APC p.A1492Cfs*22 7.06 5:112175760-112175760 P019 TP53 p.Q192* 6.77 17:7578274-7578275 P020 KRAS p.G12D 25.90 12:25398283-25398284 P020 TP53 p.C176G 24.89 17:7578403-7578404 P020 APC p.I1401Lfs*14 21.83 5:112175490-112175491 P020 CDH23 p.R1215C 15.64 10:73490288-73490289 P020 RHOA p.A61V 12.77 3:49405955-49405956 P020 PIK3R2 p.E408K 12.50 19:18273888-18273889 P020 RET p.A855S 11.76 10:43615148-43615149 P020 TERT NA 8.80 5:1298934-1298935 P020 RICTOR p.T1198I 7.69 5:38950356-38950357 P020 FBXW7 p.R465H 4.98 4:153249383-153249384 P021 PCLO p.S5089R 10.30 7:82389975-82389976 P021 APC p.T1556Nfs*3 7.03 5:112175951-112175951 P021 EPHA3 p.V73F 6.95 3:89259072-89259073 P021 DDR2 p.S469L 6.47 1:162740203-162740204 P021 KRAS p.G12V 5.88 12:25398283-25398284

P021 INHBA p.R377H 5.83 7:41729398-41729399 P021 TP53 p.W53* 5.73 17:7579527-7579528 P021 EPHA3 p.D604Y 5.59 3:89462337-89462338 P021 BRCA2 p.Q2009E 1.02 13:32914516-32914517 P022 KRAS p.G12V 4.53 12:25398283-25398284 P022 TP53 p.P177_C182del 1.41 17:7578383-7578401 P023 APC p.R1114* 18.23 5:112174630-112174631 P023 TP53 p.P47Rfs*76 15.22 17:7579546-7579547 P023 TTF2 p.R924H 9.99 1:117634537-117634538 P023 EPHA5 p.M987K 6.41 4:66197738-66197739 P023 PDGFRA p.V824I 6.06 4:55152037-55152038 P023 DNMT3A p.I705T 1.59 2:25463567-25463568 P023 CDH23 p.N667T 1.22 10:73447416-73447417 P023 CRYBG3 p.L2560M 1.10 3:97614905-97614906 P023 PDILT p.L148V 0.75 16:20387490-20387491 P023 MET p.R739H 0.61 7:116398625-116398626 P024 KIAA1191 p.P60T 6.16 5:175782602-175782603 P025 IL7R p.V11F 42.50 5:35857109-35857110 P025 FBXW7 p.R479Q 38.50 4:153247365-153247366 P025 APC p.Q1378* 26.00 5:112175422-112175423 P025 KRAS p.G12R 25.40 12:25398284-25398285 P025 APC p.R213* 17.40 5:112116591-112116592 P025 RB1 p.R552* 1.70 13:48955537-48955538 P026 TP53 p.R248Q 32.89 17:7577537-7577538 P026 PSMB5 p.P12L 27.92 14:23504055-23504056 P026 KRAS p.G12S 24.65 12:25398284-25398285 P026 APC p.Y935Ifs*19 16.82 5:112174090-112174094 P026 APC p.Q1447* 9.89 5:112175629-112175630 P026 CDKN2A p.R80* 0.31 9:21971119-21971120 P027 APC p.T1556Nfs*3 40.88 5:112175951-112175951 P027 NTRK3 p.A555D 25.74 15:88483905-88483906 P027 ABL1 p.F66L 18.89 9:133729568-133729569 P027 TP53 p.I254[2>1] 17.15 17:7577514-7577517 P027 EPHA2 p.G620R 14.81 1:16459981-16459982 P027 NTRK3 p.D537H 12.99 15:88483960-88483961 P027 NOTCH4 NA 6.08 6:32185750-32185775 P027 DNMT3A p.W117* 1.00 2:25470555-25470556 P027 KDR p.M336L 0.50 4:55976905-55976906 P027 FOXA1 p.Y166* 0.47 14:38061490-38061491 P027 ALK p.V1023L 0.46 2:29449787-29449788 P027 NTRK1 p.V105E 0.46 1:156836745-156836746 P028 TERT N 1.00 5:1300422-1300423 P028 RNF43 p.A169T 0.90 17:56440712-56440713 P028 MLL p.L991I 0.80 11:118344844-118344845 P028 PRKAA1 p.Q77R 0.70 5:40777585-40777586 P028 ERBB2 p.V842I 0.50 17:37881331-37881332 P028 PTCH1 p.D951N 0.50 9:98221917-98221918 P029 KRAS p.G12C 41.09 12:25398284-25398285 P029 TP53 p.L145del 32.21 17:7578494-7578497 P029 APC p.S1495Vfs*12 30.27 5:112175771-112175772 P029 SMO p.H760Y 16.58 7:128852205-128852206 P029 APC p.K1053Nfs*3 14.00 5:112174444-112174445 P029 SH3PXD2A p.R119Q 2.56 10:105484069-105484070 P029 BTK p.A638V 1.63 X:100604939-100604940

P029 CDH23 p.E2109Q 1.20 10:73553009-73553010 P029 PDGFRB p.E490V 1.08 5:149509429-149509430 P029 ERBB3 NA 0.90 12:56493620-56493621 P030 ARHGAP35 p.F1324C 5.09 19:47492866-47492867 P030 WDR52 p.P480L 4.13 3:113119426-113119427 P030 TP53 p.L130V 3.80 17:7578541-7578542 P030 PIK3CA p.E545K 2.96 3:178936090-178936091 P030 MAP3K1 p.Q624E 2.86 5:56171041-56171042 P030 PTPRD p.P814S 0.57 9:8492888-8492889 P031 CNOT4 p.A562T 7.92 7:135048761-135048762 P031 NRAS p.Q61K 5.88 1:115256529-115256530 P031 EXOC6 p.A43V 0.59 10:94653131-94653132 P031 IRS2 p.R832H 0.52 13:110435905-110435906 P032 MTOR p.A1699T 1.20 1:11199395-11199396 P032 FLT1 p.S796* 0.73 13:28913405-28913406 P032 TP53 p.Y220C 0.63 17:7578189-7578190 P032 BRD4 p.L92V 0.61 19:15383636-15383637 P033 TP53 p.R282W 63.80 17:7577093-7577094 P033 APC p.Q1447* 38.20 5:112175629-112175630 P033 CTNNB1 NA 37.80 3:41278077-41278078 P033 PIK3CA p.E545K 37.70 3:178936090-178936091 P033 KRAS p.Q61R 37.60 12:25380275-25380276 P033 KDR p.A1127D 36.70 4:55955564-55955565 P033 NRAS p.G13D 36.30 1:115258743-115258744 P033 KDR p.N175T 5.97 4:55981174-55981175 P033 EPHA5 p.E631D 0.93 4:66233105-66233106 P033 EZH2 p.N673K 0.82 7:148507434-148507435 P033 EPHA5 p.E632* 0.79 4:66233104-66233105 P033 GNAS p.P141S 0.70 20:57428740-57428741 P033 DNMT3A p.I32S 0.58 2:25471098-25471099 P033 OR5L2 p.I228L 0.53 11:55595375-55595376 P034 KRAS p.G12S 3.30 12:25398284-25398285 P034 EPHA2 p.V763M 0.80 1:16458596-16458597 P035 MLL p.D433Y 1.42 11:118343170-118343171 P035 EPHA3 p.N79T 1.08 3:89259091-89259092 P035 KRAS p.G12V 1.03 12:25398283-25398284 P035 DDR2 p.K763T 1.03 1:162748373-162748374 P035 TRIM58 p.F329L 0.83 1:248039314-248039315 P035 OR4C6 p.V31A 0.82 11:55432733-55432734 P035 TP53 p.V172F 0.78 17:7578415-7578416 P035 MYD88 p.R2* 0.57 3:38180155-38180156 P035 ROS1 p.E1580K 0.55 6:117662726-117662727 P036 MLL3 p.G3931R 79.60 7:151853310-151853311 P036 TP53 p.C275F 57.73 17:7577113-7577114 P036 KRAS p.G12D 42.76 12:25398283-25398284 P036 PMS2 p.E5* 41.31 7:6048637-6048638 P036 APC p.I1008Nfs*3 37.53 5:112174309-112174309 P036 PIK3CA p.Q546K 34.74 3:178936093-178936094 P036 CNOT3 p.S245Qfs*8 31.05 19:54649666-54649666 P036 FLT4 NA 24.46 5:180045767-180045768 P036 APC p.R653W 21.45 5:112170860-112170861 P036 FAT1 p.Y468H 19.38 4:187629579-187629580 P036 RET p.D567E 18.17 10:43608352-43608353 P036 ERBB3 p.G325V 17.92 12:56482425-56482426

P037 PDGFRB p.V633I 0.63 5:149504304-149504305 P037 NOTCH4 p.R130G 0.48 6:32190350-32190351 P037 PTCH2 p.A463T 0.43 1:45294730-45294731 P038 APC p.R302* 1.10 5:112151260-112151261 P039 APC p.S1465Wfs*3 2.02 5:112175675-112175677 P039 APC p.E893* 1.64 5:112173967-112173968 P039 TP53 p.P151R 1.39 17:7578477-7578478 P039 KRAS p.G12D 1.30 12:25398283-25398284 P039 FGFR3 p.G54R 0.97 4:1801030-1801031 P039 TERT NA 0.65 5:1300309-1300310 P040 FLCN p.W169* 3.30 17:17127347-17127348 P040 AXL p.L632F 2.80 19:41758839-41758840 P040 TP53 p.R196P 2.50 17:7578261-7578262 P040 EGFR p.V524F 2.40 7:55229262-55229263 P040 RET p.E136K 2.20 10:43597857-43597858 P040 APC p.R1450* 1.20 5:112175638-112175639 P041 TP53 p.G245S 86.63 17:7577547-7577548 P041 APC p.W593* 70.21 5:112170681-112170682 P041 KRAS p.G12V 21.78 12:25398283-25398284 P041 APC p.S1415Rfs*4 13.57 5:112175535-112175536 P041 APC p.S2724T 8.41 5:112179460-112179461 P041 MAP2K4 p.R228K 5.86 17:12013740-12013741 P041 MAP2K1 p.K57T 5.28 15:66727453-66727454 P041 MSH6 p.Q1328* 4.40 2:48033770-48033771 P041 CDK13 NA 3.79 7:40027195-40027196 P041 KRAS p.Q61H 2.21 12:25380274-25380275 P041 ABL1 p.E883G 2.10 9:133760324-133760325 P041 ITM2A p.F108V 1.71 X:78618557-78618558 P041 EGFR p.V441D 1.59 7:55227854-55227855 P041 INPP4B p.K910T 1.32 4:142949980-142949981 P041 NF1 p.S2288T 1.27 17:29667525-29667526 P041 INHBA p.F138I 1.18 7:41730116-41730117 P041 INHBA p.H137Q 1.18 7:41730117-41730118 P041 MLH3 p.Q917H 1.04 14:75513607-75513608 P041 NAV3 p.P403L 1.00 12:78400525-78400526 P041 PTCH1 p.L596R 0.90 9:98232154-98232155 P041 EPHA3 p.K800T 0.87 3:89498426-89498427 P041 NOTCH4 p.E1373D 0.87 6:32168913-32168914 P041 BRCA2 p.T665I 0.80 13:32910485-32910486 P041 CDKN2A p.S73R 0.79 9:21971183-21971184 P041 MSH6 p.K1296T 0.76 2:48033675-48033676 P041 CDH1 p.K109T 0.74 16:68835734-68835735 P041 HDAC1 p.V224L 0.71 1:32794701-32794702 P041 MS4A1 p.S289A 0.68 11:60235911-60235912 P041 KRAS p.E63D 0.62 12:25380268-25380269 P041 EGFR p.S464L 0.59 7:55227923-55227924 P042 TP53 NA 46.03 17:7578289-7578290 P042 KRAS p.A146T 38.94 12:25378561-25378562 P042 HIST1H3B p.Q126P 28.81 6:26031911-26031912 P042 KEAP1 p.C273R 16.30 19:10602760-10602761 P043 KRAS p.G13D 49.70 12:25398280-25398281 P043 AKT1 p.E17K 39.50 14:105246550-105246551 P043 FAM5C p.I627N 5.00 1:190067568-190067569 P043 ABCC11 p.T893M 0.90 16:48226458-48226459

P043 C11orf30 p.P253Q 0.70 11:76175050-76175051 P043 CDK6 p.R131* 0.60 7:92355085-92355086 P043 HCLS1 p.L352F 0.60 3:121351364-121351365 P043 IRS2 p.R1020C 0.60 13:110435342-110435343 P043 PDGFRA p.S1013R 0.60 4:55156637-55156638 P043 BRD4 p.R1274W 0.50 19:15349753-15349754 P043 MAP3K1 p.P962H 0.50 5:56177911-56177912 P043 SETD2 p.T444M 0.50 3:47164794-47164795 P043 EPHA2 p.R384C 0.40 1:16464509-16464510 P044 PTPRD p.R229Q 0.65 9:8523517-8523518 P044 DNMT3A p.H550P 0.49 2:25463276-25463277 P045 APC p.R232* 17.30 5:112128190-112128191 P045 APC p.R216* 15.20 5:112128142-112128143 P046 PIK3CA p.Q546K 20.50 3:178936093-178936094 P046 NLRP4 p.V809M 15.20 19:56382262-56382263 P046 APC p.T1556Nfs*3 14.10 5:112175951-112175951 P046 KDR p.E1203A 13.80 4:55953827-55953828 P046 KRAS p.G12D 13.60 12:25398283-25398284 P046 TSC2 p.R976W 12.90 16:2127686-2127687 P046 FLT3 p.I687N 8.10 13:28601371-28601372 P046 MSH2 p.S699L 1.00 2:47703595-47703596 P046 CDK13 p.K472N 0.70 7:40027401-40027402 P046 MSH6 p.S341C 0.70 2:48026143-48026144 P046 ALK p.R292H 0.50 2:29917792-29917793 P046 ACIN1 p.R192L 0.30 14:23533326-23533327 P046 CRKL p.R183* 0.20 22:21288301-21288302 P046 FGFR2 p.R255W 0.20 10:123279668-123279669 P047 MSH2 p.K918N 6.36 2:47710036-47710037 P047 FAT1 p.E3124K 6.33 4:187534355-187534356 P047 MAP3K1 p.S1330L 5.56 5:56181764-56181765 P047 RB1 p.E927D 5.09 13:49054200-49054201 P047 ATR p.E323D 4.97 3:142281274-142281275 P047 IL7R p.D364Y 4.86 5:35876297-35876298 P047 SLC4A10 p.F400C 4.85 2:162751192-162751193 P047 CCNE1 p.F172L 4.84 19:30311661-30311662 P047 FLT3 p.L262I 4.83 13:28623869-28623870 P047 HGF p.P325T 4.81 7:81358987-81358988 P047 CDH18 p.R638H 4.77 5:19473794-19473795 P047 CDH18 p.K640T 4.63 5:19473788-19473789 P047 APC p.R2204* 4.52 5:112177900-112177901 P047 APC p.E1544* 4.51 5:112175920-112175921 P047 APC p.R2237* 4.51 5:112177999-112178000 P047 PDGFRA p.E36D 4.51 4:55127319-55127320 P047 BRCA2 p.K1351T 4.40 13:32912543-32912544 P047 BRCA2 p.S3147Y 4.36 13:32969008-32969009 P047 ERBB3 p.A232V 4.28 12:56481659-56481660 P047 RB1 p.E237* 4.23 13:48934253-48934254 P047 RET p.A35V 4.21 10:43595936-43595937 P047 OR5L2 p.I258M 4.18 11:55595467-55595468 P047 BRCA1 p.E203* 4.12 17:41247925-41247926 P047 EPHA3 p.E265* 4.10 3:89259648-89259649 P047 BRAF p.F68C 4.06 7:140549947-140549948 P047 APC p.A1582V 4.02 5:112176035-112176036 P047 GATA3 p.Q297H 4.02 10:8106067-8106068

P047 KIT p.E366D 3.98 4:55573435-55573436 P047 CDK12 p.N3T 3.98 17:37618331-37618332 P047 EGFR p.F968L 3.92 7:55268063-55268064 P047 EGFR p.R932C 3.89 7:55266501-55266502 P047 ATM p.R805* 3.87 11:108129748-108129749 P047 BRCA2 p.F439V 3.86 13:32906929-32906930 P047 CDH1 p.L311F 3.79 16:68845684-68845685 P047 PIK3CA p.Y1021C 3.78 3:178952006-178952007 P047 BRCA2 p.N2119H 3.69 13:32914846-32914847 P047 DDR2 p.S208Y 3.66 1:162725510-162725511 P047 ERBB3 p.K314T 3.66 12:56482392-56482393 P047 NAV3 p.E572D 3.65 12:78401033-78401034 P047 FAM5C p.E582D 3.64 1:190067702-190067703 P047 KRAS p.K170T 3.62 12:25368435-25368436 P047 FAT1 p.R1627* 3.61 4:187542860-187542861 P047 NOTCH2 p.P2087S 3.60 1:120459085-120459086 P047 ENPP2 p.R446* 3.59 8:120602771-120602772 P047 CBL p.R788Q 3.58 11:119169178-119169179 P047 ATM p.R692H 3.57 11:108124716-108124717 P047 ATR p.R162I 3.56 3:142281758-142281759 P047 SH3PXD2A p.E116K 3.54 10:105484079-105484080 P047 ERBB4 p.E100D 3.53 2:212812275-212812276 P047 BCR p.E691D 3.52 22:23615918-23615919 P047 XPO1 p.E1068* 3.52 2:61705968-61705969 P047 ABCC11 p.E1169K 3.50 16:48210867-48210868 P047 SLC43A1 p.E220K 3.50 11:57263537-57263538 P047 NRAS p.E132K 3.49 1:115252245-115252246 P047 CBL p.Y368C 3.49 11:119148882-119148883 P047 RARB p.K121N 3.49 3:25542728-25542729 P047 PDGFRA p.D173N 3.47 4:55129982-55129983 P047 EPHA5 p.E1025* 3.47 4:66189872-66189873 P047 SETD2 p.L1357I 3.46 3:47162056-47162057 P047 CDKN1B p.E71* 3.43 12:12870983-12870984 P047 KRAS p.G12D 3.43 12:25398283-25398284 P047 PTEN p.R130Q 3.43 10:89692904-89692905 P047 MPL p.F41L 3.41 1:43803812-43803813 P047 BRCA2 p.D559Y 3.38 13:32907289-32907290 P047 MPL p.C291Y 3.38 1:43806075-43806076 P047 RET p.L1101F 3.37 10:43623672-43623673 P047 TRPC5 p.Y14H 3.37 X:111195608-111195609 P047 CDH23 p.D1739N 3.36 10:73539050-73539051 P047 COL4A5 p.G469* 3.36 X:107834855-107834856 P047 AKT3 p.D362A 3.34 1:243716108-243716109 P047 FAT1 p.R132Q 3.34 4:187630586-187630587 P047 PTPRD p.S1816F 3.34 9:8331668-8331669 P047 OR5L2 p.F71L 3.34 11:55594906-55594907 P047 NTRK3 p.Q159H 3.32 15:88680779-88680780 P047 ALK p.R401* 3.30 2:29606678-29606679 P047 RB1 p.E677* 3.29 13:49033891-49033892 P047 C1S p.R578C 3.28 12:7177619-7177620 P047 FLT1 p.R1026I 3.28 13:28895696-28895697 P047 NTRK1 p.E354K 3.27 1:156843723-156843724 P047 USP48 p.K308N 3.27 1:22073626-22073627 P047 SH3BGR p.D96N 3.27 21:40834351-40834352

P047 NUP205 p.K156N 3.26 7:135261141-135261142 P047 FAT1 p.I1659L 3.25 4:187542764-187542765 P047 FLCN p.P187S 3.24 17:17127294-17127295 P047 FBXW7 p.0? 3.23 4:153332952-153332953 P047 OR6F1 p.F177L 3.23 1:247875526-247875527 P047 SAFB2 p.E73* 3.21 19:5621376-5621377 P047 ATM p.T2947A 3.21 11:108225589-108225590 P047 FLT1 p.K60T 3.21 13:29041248-29041249 P047 BRCA2 p.H1085N 3.19 13:32911744-32911745 P047 MYH4 p.R275Q 3.14 17:10366486-10366487 P047 FAM5C p.M497I 3.13 1:190067957-190067958 P047 DDR2 p.R105H 3.11 1:162724541-162724542 P047 XPO1 p.E571K 3.08 2:61719471-61719472 P047 NF1 p.N78H 3.08 17:29486054-29486055 P047 COL19A1 p.M105V 3.08 6:70637846-70637847 P047 NTRK3 p.K822N 3.05 15:88420219-88420220 P047 BRCA2 p.E1518* 3.03 13:32913043-32913044 P047 CDH23 NA 3.01 10:73548799-73548800 P047 ATR p.G882* 2.79 3:142272229-142272230 P047 INPP4B p.E285* 2.77 4:143130162-143130163 P047 MSH3 p.E238* 2.33 5:79966047-79966048 P047 NF1 p.R2429* 1.80 17:29677226-29677227 P048 RAF1 p.S428I 0.70 3:12632383-12632384 P049 KRAS p.G12A 4.30 12:25398283-25398284 P049 APC p.E1317* 2.70 5:112175239-112175240 P049 KIAA1199 p.R754Q 2.30 15:81217019-81217020 P049 FGFR2 p.D321E 2.00 10:123276953-123276954 P049 TP53 p.S94* 1.50 17:7579405-7579406 P049 TP53 p.S95T 1.50 17:7579403-7579404 P049 HIST1H3B p.K38R 0.50 6:26032175-26032176 P049 MTOR p.G2486S 0.50 1:11169418-11169419 P049 NOTCH4 p.R471H 0.20 6:32187466-32187467 P050 APC p.E1550Rfs*15 37.24 5:112175936-112175937 P050 TP53 p.K132N 33.54 17:7578533-7578534 P050 APC p.R283* 24.15 5:112151203-112151204 P050 CDH23 p.N1245S 19.46 10:73491761-73491762 P050 KEAP1 p.G462R 1.28 19:10600470-10600471 P050 EPHA3 NA 1.15 3:89468353-89468354 P051 GAB2 p.S359N 6.90 11:77937641-77937642 P051 FLT4 p.A360V 4.60 5:180055905-180055906 P051 CSMD3 p.T750M 4.30 8:113697867-113697868 P051 TP53 p.C275Vfs*70 4.10 17:7577114-7577115 P051 RNF43 p.M203Rfs*9 3.10 17:56439983-56439984 P051 KRTAP5-5 p.Y192del 2.00 11:1651644-1651644 P051 PPP1R17 p.P63Tfs*25 1.50 7:31735178-31735178 P051 TMEM247 p.Q152_Q153ins 1.30 2:46707878-46707878 P051 BRAF p.V600E 1.20 7:140453135-140453136 P051 CDH23 p.A1222T 0.80 10:73490309-73490310 P051 ROBO3 p.P457Q 0.80 11:124742818-124742819 P051 MLL4 p.I2694M 0.60 19:36229391-36229392 P052 DNMT3A p.R201C 43.30 2:25497847-25497848 P052 RET p.G568S 38.20 10:43608353-43608354 P052 KRAS p.A146V 37.73 12:25378560-25378561 P052 APC p.S1415* 29.80 5:112175533-112175533

P052 FBXW7 p.A503T 24.40 4:153247294-153247295 P052 APC p.Q1131* 21.60 5:112174681-112174682 P052 CDK13 p.S250[5>4] 1.20 7:39990985-39990988 P052 FCGR3A p.K249M 0.90 1:161512820-161512821 P052 MDM2 p.V492L 0.90 12:69233608-69233609 P052 NOTCH1 p.C838S 0.40 9:139405678-139405679 P053 TP53 p.C238Y 3.40 17:7577567-7577568 P053 FBXW7 p.R465H 0.80 4:153249383-153249384 P054 ABL2 p.A983V 0.50 1:179077453-179077454 P055 CSF1R p.G798R 70.60 5:149435831-149435832 P055 APC p.A1492Cfs*22 62.20 5:112175760-112175760 P055 TP53 p.R213* 55.50 17:7578211-7578212 P055 KRAS p.G12D 33.20 12:25398283-25398284 P055 PIK3CA p.P104_G106del 20.00 3:178916922-178916931 P055 IRS2 p.K81R 9.30 13:110438158-110438159 P055 EPHA5 p.N805K 5.58 4:66217199-66217200 P055 APC p.R805* 4.08 5:112173703-112173704 P056 TP53 p.R175H 69.90 17:7578405-7578406 P056 BCR p.R1081Q 45.60 22:23653942-23653943 P056 APC p.W421* 34.00 5:112154991-112154992 P056 APC p.E1309Dfs*4 31.33 5:112175211-112175216 P056 COL1A1 NA 2.42 17:48267902-48267903 P057 TMPRSS2 p.V197M 0.40 21:42852496-42852497 P057 NOTCH4 p.P204L 0.30 6:32188942-32188943 P058 KEAP1 p.A607T 0.68 19:10597383-10597384 P058 NOTCH1 p.D260N 0.60 9:139413981-139413982 P059 APC p.W421* 47.00 5:112154990-112154991 P059 TP53 p.E286Sfs*56 45.50 17:7577072-7577082 P059 NF2 p.A405Qfs*23 35.20 22:30069341-30069341 P060 TP53 p.R175H 61.43 17:7578405-7578406 P060 KRAS p.G12A 41.38 12:25398283-25398284 P060 OBP2A p.D116Y 3.06 9:138439784-138439785 P060 HGF p.F99L 1.28 7:81388077-81388078 P060 FOXA1 p.Q263R 1.07 14:38061200-38061201 P060 ERBB4 p.A769S 0.61 2:212426809-212426810 P061 HDAC4 p.R253W 0.48 2:240066386-240066387 P061 AKT1 p.T443M 0.35 14:105237116-105237117 P062 COL9A1 p.E842G 0.43 6:70935690-70935691 P063 APC NA 6.62 5:112155042-112155043 P063 TP53 p.S166* 4.60 17:7578432-7578433 P063 SMARCA4 p.R1135L 4.17 19:11141426-11141427 P063 APC p.R876* 3.76 5:112173916-112173917 P063 NRAS p.Q61K 3.43 1:115256529-115256530 P063 AXL p.T112M 3.30 19:41727076-41727077 P063 ALK p.V712M 3.27 2:29474040-29474041 P064 KRAS p.G12D 17.90 12:25398283-25398284 P064 IRS2 p.R261H 0.60 13:110437618-110437619 P065 ALK p.R1113W 21.78 2:29446229-29446230 P065 TP53 p.T211Ffs*4 21.38 17:7578216-7578218 P065 OR4A15 p.K118R 17.63 11:55135711-55135712 P065 APC p.R213* 16.20 5:112116591-112116592 P065 CSMD1 p.R1724H 14.18 8:3057258-3057259 P065 ERBB3 p.P554L 11.14 12:56487929-56487930 P065 FLT3 p.K108* 7.18 13:28636049-28636050

P065 APC p.R232Yfs*21 7.18 5:112128186-112128186 P065 POM121L12 p.S153Y 6.46 7:53103821-53103822 P065 ARAF p.K551R 1.24 X:47430376-47430377 P065 ROCK1 p.S576T 1.15 18:18586469-18586470 P065 ROCK1 p.E570* 0.87 18:18586488-18586489 P066 TP53 p.G245S 24.49 17:7577547-7577548 P066 KRAS p.G13D 22.59 12:25398280-25398281 P066 FBXW7 p.R465C 10.15 4:153249384-153249385 P066 MITF p.R214* 9.69 3:70005610-70005611 P066 SETD2 p.I2411T 5.87 3:47084056-47084057 P066 MLH3 p.P1402Q 3.01 14:75485568-75485569 P067 KRAS p.G13C 8.81 12:25398281-25398282 P067 APC p.S770* 5.86 5:112173599-112173600 P068 APC p.S1426Rfs*2 0.40 5:112175568-112175568 P069 IL1RAPL1 p.L348I 5.30 X:29938195-29938196 P069 FLT4 p.D1270G 3.10 5:180036051-180036052 P069 TP53 p.G245S 2.90 17:7577547-7577548 P069 NF1 p.K1345* 2.20 17:29576059-29576060 P069 RNF43 p.Q333Kfs*86 2.20 17:56436140-56436141 P069 FGFR1 p.E467K 1.50 9:38275776-38275777 P069 ROS1 p.K1081T 0.80 6:117683904-117683905 P070 IL1RAPL1 p.L348I 27.00 X:29938195-29938196 P070 TP53 p.G245S 14.40 17:7577547-7577548 P070 FLT4 p.D1270G 12.05 5:180036051-180036052 P070 RNF43 p.Q333Kfs*86 11.39 17:56436139-56436140 P070 NF1 p.K1345* 8.66 17:29576059-29576060 P070 FGFR1 p.E467K 6.99 8:38275776-38275777 P070 ROS1 p.K1081T 3.63 6:117683904-117683905 P071 TP53 NA 17.50 17:7579591-7579592 P071 APC p.E1464Vfs*8 11.89 5:112175675-112175679 P071 APC NA 6.38 5:112116485-112116486 P071 ABL1 p.R552K 6.16 9:133755970-133755971 P072 TP53 p.K132N 3.08 17:7578533-7578534 P072 STK11 NA 1.48 19:1220504-1220505 P072 RARA p.R114H 0.48 17:38506048-38506049 P072 SMARCA4 p.R885H 0.46 19:11132437-11132438 P073 TP53 p.P98R 35.49 17:7579393-7579394 P073 APC p.E1379* 32.85 5:112175425-112175426 P073 KRAS p.G13D 24.43 12:25398280-25398281 P073 PIK3CA p.E542K 11.67 3:178936081-178936082 P073 STAT1 p.V455I 10.29 2:191848450-191848451 P073 ATP2C1 NA 9.40 3:130714955-130714956 P074 TP53 p.V157D 85.81 17:7578459-7578460 P074 KRAS p.G12V 60.84 12:25398283-25398284 P074 APC p.P1467Tfs*2 51.21 5:112175688-112175688 P074 APC p.S770* 29.29 5:112173599-112173600 P074 TMPRSS2 p.S473F 13.99 21:42840329-42840330 P074 BRCA2 p.Y2977H 6.28 13:32953627-32953628 P074 MPL p.Q255H 4.18 1:43805708-43805709 P074 ABL1 p.G555D 3.95 9:133756036-133756037 P074 NF2 p.Y244C 3.32 22:30057248-30057249 P074 NF2 p.E247Gfs*14 2.38 22:30057256-30057256 P074 TGFBR1 p.K337M 2.16 9:101907049-101907050 P075 EPHB1 p.E341Q 7.50 3:134851614-134851615

P075 XPO1 p.N719Y 6.00 2:61715773-61715774 P075 CBLB p.A937T 5.10 3:105377953-105377954 P075 SLIT2 p.L1366H 1.40 4:20618781-20618782 P075 APC p.D2016N 0.90 5:112177336-112177337 P075 ESR1 p.G344V 0.90 6:152265577-152265578 P075 MEN1 p.R332H 0.90 11:64573757-64573758 P075 LRP1B p.P4512T 0.70 2:140995746-140995747 P075 IGF1R p.Q710R 0.50 15:99460032-99460033 P075 BRCA1 p.S850C 0.40 17:41244999-41245000 P076 TP53 p.I195T 9.50 17:7578264-7578265 P076 ALK p.S737L 6.80 2:29462690-29462691 P076 BRAF p.V600E 6.10 7:140453135-140453136 P076 PIK3CA p.E545D 4.10 3:178936092-178936093 P076 PTCH2 p.H783L 0.30 1:45293096-45293097 P077 TP53 p.G245S 0.59 17:7577547-7577548 P078 TERT NA 0.30 5:1299755-1299756 P079 APC p.D209Efs*10 36.65 5:112116581-112116582 P079 TP53 p.P191Sfs*55 20.20 17:7578274-7578278 P079 GNAS p.G456R 6.68 20:57429685-57429686 P079 PKLR p.R149W 2.64 1:155265289-155265290 P080 PIK3CA p.E545K 8.20 3:178936090-178936091 P080 KRAS p.G12D 7.96 12:25398283-25398284 P080 ERBB4 p.K682T 4.11 2:212495220-212495221 P080 APC p.E1464* 2.83 5:112175680-112175681 P080 ATM p.K1807Dfs*15 2.81 11:108173677-108173679 P080 PTPRD p.E675* 0.68 9:8500858-8500859 P080 DNMT3A p.I580V 0.68 2:25463187-25463188 P081 KRAS p.G13D 14.95 12:25398280-25398281 P081 ERBB2 p.G776V 6.21 17:37880997-37880998 P081 APC p.H1172Vfs*11 3.28 5:112174802-112174802 P081 RET NA 3.08 10:43608411-43608412 P081 TP53 p.R273P 2.79 17:7577119-7577120 P081 CSMD3 p.D754Y 1.12 8:113697856-113697857 P081 FAT1 p.N3945S 0.65 4:187521320-187521321 P082 KRAS p.Q61H 36.65 12:25380274-25380275 P082 TP53 p.P151S 23.13 17:7578478-7578479 P082 EPHA5 p.G1033R 14.30 4:66189848-66189849 P082 IRS2 p.C1306G 2.82 13:110434484-110434485 P082 NTRK1 p.G191A 2.33 1:156838383-156838384 P082 ESR1 p.G90S 0.96 6:152129314-152129315 P083 TP53 p.F134L 56.38 17:7578529-7578530 P083 MTOR p.E1799K 43.21 1:11190803-11190804 P083 MLL3 p.G4692S 40.86 7:151842337-151842338 P083 APC p.T1556Nfs*3 38.98 5:112175951-112175951 P083 KRAS p.G13D 31.51 12:25398280-25398281 P083 PIK3CA p.H419_P421delinsT 26.10 3:178927976-178927983 P084 MED12 p.R418H 1.20 X:70342361-70342362 P084 BRD4 p.V468M 0.51 19:15367923-15367924 P084 FGFR3 p.R175H 0.39 4:1803171-1803172 P084 FOXA1 p.A121V 0.35 14:38061626-38061627 P085 KRAS p.G12D 1.94 12:25398283-25398284 P085 APC p.V1414* 1.20 5:112175529-112175530 P085 CBL p.V431A 1.18 11:119149283-119149284 P085 DNMT3A p.R693C 0.98 2:25457242-25457243

P085 DNMT3A p.V527I 0.75 2:25463535-25463536 P086 APC p.Q1378* 1.60 5:112175422-112175423 P087 DNMT3A p.F225I 0.87 2:25469527-25469528 P087 DNMT3A p.R137C 0.46 2:25470497-25470498 P088 CDK4 p.G111A 0.40 12:58145011-58145012 P089 NOTCH3 p.L1038S 0.70 19:15291520-15291521 P090 BRAF p.D594G 3.50 7:140453153-140453154 P090 NRAS p.G13V 2.40 1:115258743-115258744 P090 DNMT3A p.R771* 1.40 2:25463181-25463182 P090 FLT4 p.A1143T 1.30 5:180040014-180040015 P090 DNMT3A p.V657M 1.00 2:25464543-25464544 P090 CDH23 p.A2753T 0.60 10:73567111-73567112 P090 MLL p.V2963E 0.60 11:118375494-118375495 P090 NOTCH4 p.M845I 0.60 6:32180395-32180396 P090 NOTCH4 p.R1652L 0.60 6:32165172-32165173 P091 CDH23 p.G165Afs*25 0.69 10:73326558-73326559 P092 APC p.R1640W 1.40 5:112176208-112176209 P092 APC p.E902* 1.20 5:112173994-112173995 P092 KRAS p.G12V 1.20 12:25398283-25398284 P092 CDH23 p.E2044K 0.90 10:73550968-73550969 P092 CDH23 p.P2380L 0.90 10:73558951-73558952 P092 CDH23 p.R2358Q 0.80 10:73558885-73558886 P092 ATR p.M211T 0.70 3:142281611-142281612 P092 TRIM58 p.V322I 0.60 1:248039293-248039294 P092 APC p.A2118[5>4] 0.40 5:112177642-112177645 P092 FCGR2A p.H166R 0.40 1:161479744-161479745 P092 POM121L12 p.Q64E 0.40 7:53103553-53103554 P093 APC p.R1450* 23.20 5:112175638-112175639 P093 TP53 p.R181P 20.90 17:7578387-7578388 P093 RICTOR p.S1122C 5.40 5:38950584-38950585 P093 BRD2 p.L381R 1.10 6:32944654-32944655 P093 MLH3 p.R1251W 0.80 14:75498846-75498847 P093 AXL p.A461T 0.70 19:41748855-41748856 P093 KDR p.A467V 0.70 4:55973915-55973916 P093 PTPN11 p.E76A 0.70 12:112888210-112888211 P093 TERT NA 0.60 5:1300490-1300491 P093 MYC p.P58R 0.20 8:128750635-128750636 P093 MYC p.S79R 0.20 8:128750699-128750700 P093 MYC p.P213T 0.20 8:128751099-128751100 P093 PIK3CB p.G950V 0.20 3:138376624-138376625 P093 PIK3CB p.R955* 0.20 3:138376610-138376611 P093 PIK3CB p.E294* 0.20 3:138453567-138453568 P093 MYC p.A200T 0.10 8:128751060-128751061 P093 PIK3CB NA 0.10 3:138376529-138376530 P093 PIK3CB p.R995W 0.10 3:138375075-138375076 P094 MTOR p.E1799K 16.40 1:11190803-11190804 P094 TP53 p.M237I 16.40 17:7577569-7577570 P094 KRAS p.G13D 13.00 12:25398280-25398281 P094 AKT1 p.E17K 12.50 14:105246550-105246551 P094 DNMT3A p.K826Sfs*5 1.10 2:25459807-25459808 P095 ROS1 p.A197T 0.79 6:117718267-117718268 P095 BCL2 p.L181P 0.60 18:60985357-60985358 P096 DNMT3A p.V716I 1.90 2:25463535-25463536 P096 FBXW7 p.S582L 0.70 4:153245445-153245446

P097 KRAS p.G13D 11.60 12:25398280-25398281 P097 TP53 p.R282W 11.10 17:7577093-7577094 P097 APC p.A1351Sfs*3 8.70 5:112175338-112175338 P097 APC p.R283* 8.30 5:112151203-112151204 P097 LRRC7 p.R5W 4.40 1:70225899-70225900 P098 ESR1 p.S566I 5.30 6:152420009-152420010 P098 PIK3CA p.R916H 5.30 3:178947871-178947872 P098 FGFR1 p.D218G 5.10 8:38283731-38283732 P098 HDAC4 p.R1040C 5.00 2:239975252-239975253 P098 APC p.G721* 4.70 5:112173451-112173452 P098 NOTCH3 p.R532H 4.50 19:15298702-15298703 P098 RET p.A680T 4.20 10:43610085-43610086 P098 CCNE1 p.R95Q 3.90 19:30308146-30308147 P098 SMARCA4 p.V1199A 3.90 19:11144014-11144015 P098 MLH1 p.R100* 3.80 3:37042535-37042536 P098 SYK p.L103I 3.60 9:93606486-93606487 P098 ERBB3 p.V104M 3.50 12:56478853-56478854 P098 FGFR4 p.P356H 3.10 5:176520147-176520148 P098 FLT1 p.V1162A 2.90 13:28886136-28886137 P098 MTOR p.R1683W 2.90 1:11199443-11199444 P098 PIK3CA p.E545A 2.90 3:178936091-178936092 P098 CTNNB1 p.A91T 2.60 3:41266473-41266474 P098 HDAC4 p.M28I 2.60 2:240158298-240158299 P098 C1QA p.K33I 2.50 1:22964206-22964207 P098 TSC2 p.L424P 2.40 16:2112510-2112511 P098 MSH3 p.P681A 2.30 5:80063895-80063896 P098 GNA11 p.R60H 2.20 19:3110188-3110189 P098 HRAS p.A18V 2.20 11:534269-534270 P098 FBXW7 p.R465C 1.70 4:153249384-153249385 P098 BRCA2 p.E2872D 1.50 13:32945220-32945221 P098 NOTCH1 p.V53M 1.40 9:139418414-139418415 P098 MDM2 p.R189C 1.10 12:69222591-69222592 P098 MTOR p.A469T 1.00 1:11303177-11303178 P098 PDGFRB p.A6V 1.00 5:149516593-149516594 P098 TP53 p.S240G 1.00 17:7577562-7577563 P098 AKT3 p.R247H 0.60 1:243736306-243736307 P098 BRCA2 p.A2487D 0.60 13:32930588-32930589 P098 EGFR p.A822S 0.60 7:55249165-55249166 P098 EPHA2 p.T922M 0.60 1:16455988-16455989 P098 FLT1 p.V426A 0.60 13:29001454-29001455 P098 IRS2 p.V775A 0.60 13:110436076-110436077 P098 JAK3 p.P37A 0.60 19:17955117-17955118 P098 PTCH1 p.Q1300H 0.60 9:98209637-98209638 P098 ATM p.R2060H 0.50 11:108186820-108186821 P098 MPL p.A141V 0.50 1:43804971-43804972 P098 NOTCH1 p.H2500P 0.50 9:139390691-139390692 P098 TP53 p.R273C 0.50 17:7577120-7577121 P098 APC p.S376N 0.40 5:112154855-112154856 P098 ERBB3 p.R675G 0.40 12:56489557-56489558 P098 NOTCH2 p.Y2383S 0.40 1:120458196-120458197 P098 OR11G2 p.T113P 0.40 14:20665830-20665831 P098 MLL p.S774A 0.30 11:118344193-118344194 P099 KRAS p.G12D 0.79 12:25398283-25398284 P100 APC NA 31.41 5:112116600-112116601

P100 TP53 p.G245S 23.71 17:7577547-7577548 P100 MLH1 p.I150M 18.51 3:37048550-37048551 P100 PTPN11 p.V428L 11.72 12:112924335-112924336 P101 KRAS p.G12D 39.85 12:25398283-25398284 P101 APC NA 38.50 5:112137081-112137082 P101 ROS1 p.R1948H 24.42 6:117641127-117641128 P101 ATM p.R1898* 23.83 11:108178640-108178641 P101 CSMD3 p.S1514C 17.27 8:113562922-113562923 P101 TMPRSS2 p.V197M 0.54 21:42852496-42852497 P101 RNF43 p.L418M 0.53 17:56435884-56435885 P101 AURKA p.F31I 0.48 20:54961540-54961541 P102 TP53 p.G266E 20.90 17:7577140-7577141 P102 APC p.K1308* 11.70 5:112175212-112175213 P102 TENM3 p.G60S 8.20 4:183245350-183245351 P102 RALBP1 p.K421E 8.00 18:9525762-9525763 P102 EPHA3 p.W250C 6.30 3:89259605-89259606 P102 AR p.P375L 5.30 X:66766111-66766112 P102 FAM5C p.S725T 0.40 1:190067275-190067276 P103 TP53 p.R273H 3.10 17:7577119-7577120 P103 APC p.Q260* 2.90 5:112137023-112137024 P103 GATA3 p.T108I 2.80 10:8100348-8100349 P103 KRAS p.G12V 1.70 12:25398283-25398284 P103 FBXW7 p.K604I 1.20 4:153245379-153245380 P103 APC p.Q1529* 1.10 5:112175875-112175876 P103 PIK3CA p.R38H 1.10 3:178916725-178916726 P103 FGFR3 p.A179T 0.50 4:1803182-1803183 P103 FLT4 p.R476W 0.40 5:180051056-180051057 P104 TRIM58 p.D452G 41.60 1:248039684-248039685 P104 APC p.L662Tfs*11 37.43 5:112173273-112173275 P104 SLC26A3 p.R752H 31.70 7:107408039-107408040 P104 PARP4 p.G463A 16.40 13:25058850-25058851 P104 MTOR p.N692T 7.74 1:11298032-11298033 P104 C11orf30 p.D929H 3.66 11:76255377-76255378 P104 CDH1 p.S770I 1.88 16:68863569-68863570 P104 TERT NA 0.97 5:1300702-1300703 P105 KRAS p.K170T 6.58 12:25368435-25368436 P105 KRAS p.G12A 6.25 12:25398283-25398284 P105 PIK3R1 p.E291* 5.64 5:67576788-67576789 P105 KRAS p.A146T 5.15 12:25378561-25378562 P105 TSC1 p.R500* 4.69 9:135781466-135781467 P105 TP53 p.S149Ffs*32 3.81 17:7578484-7578484 P105 MTOR p.L2427Q 3.79 1:11174394-11174395 P105 JAK1 p.R532C 3.43 1:65321245-65321246 P105 SPTA1 p.R891* 2.88 1:158627400-158627401 P105 HDAC4 p.P578L 2.54 2:240036791-240036792 P105 PIK3CA p.N345H 2.20 3:178921550-178921551 P106 HIST1H3B p.A92V 0.60 6:26032013-26032014 P107 TP53 p.R267G 13.26 17:7577138-7577139 P107 FBXW7 p.R224* 11.69 4:153268137-153268138 P107 APC p.E1309Dfs*4 11.43 5:112175211-112175216 P107 KRAS p.G12V 11.41 12:25398283-25398284 P107 PIK3R1 p.G627R 3.85 5:67592062-67592063 P107 FBXW7 p.D560Y 2.93 4:153245512-153245513 P108 HDAC4 p.D925Y 0.50 2:239990265-239990266

P109 TP53 p.R306* 24.40 17:7577021-7577022 P109 APC p.T1301Nfs*14 11.20 5:112175191-112175191 P109 IL6ST p.A664V 9.80 5:55238525-55238526 P109 APC p.R499* 9.60 5:112162890-112162891 P110 RARA p.L32Q 0.90 17:38487564-38487565 P110 IRS2 p.D562G 0.60 13:110436715-110436716 P111 APC p.R1450* 0.76 5:112175638-112175639 P111 PALB2 p.N1003D 0.46 16:23632788-23632789 P112 FAT1 p.G2934Vfs*3 0.81 4:187538940-187538941 P112 MLL p.A80T 0.77 11:118307464-118307465 P113 FAM5C p.R719H 41.40 1:190067292-190067293 P113 CTNNB1 p.S37F 35.30 3:41266112-41266113 P113 TP53 p.H168Qfs*2 32.67 17:7578425-7578426 P113 FGFR1 p.P702R 10.20 8:38271750-38271751 P113 NTRK1 p.V594M 7.93 1:156848995-156848996 P114 TP53 p.R306* 53.27 17:7577021-7577022 P114 BRAF p.V600E 45.93 7:140453135-140453136 P114 KIT p.H180L 45.26 4:55564650-55564651 P114 LRRC7 p.R10H 31.84 1:70225915-70225916 P114 EPHA3 p.E21K 31.06 3:89156958-89156959 P114 APC p.Q1193* 28.78 5:112174867-112174868 P114 AXL p.V860I 25.55 19:41765701-41765702 P114 POLE p.F366_F367delinsL 24.61 12:133252325-133252328 P114 NF2 p.F96L 19.49 22:30035125-30035126 P114 APC p.T1556Nfs*3 16.20 5:112175951-112175951 P114 MLL p.R173Q 15.33 11:118342391-118342392 P114 SETD2 p.D780A 14.22 3:47163786-47163787 P114 PTPRD p.E1309D 14.06 9:8449785-8449786 P114 MAP2K1 p.D67N 13.63 15:66727482-66727483 P114 JAK3 p.R40H 11.86 19:17955107-17955108 P114 BRCA2 p.R2318* 9.14 13:32920977-32920978 P114 BRCA2 p.A2306V 5.89 13:32918769-32918770 P114 PIK3CA p.R230* 3.79 3:178919202-178919203 P114 ABCC11 NA 3.27 16:48245110-48245111 P114 IL7R p.A432V 2.82 5:35876502-35876503 P114 ATM p.L1775S 1.96 11:108173583-108173584 P114 MLH1 p.G638R 1.89 3:37090022-37090023 P114 CCNE1 p.I193M 1.63 19:30311724-30311725 P114 MTOR NA 1.56 1:11206731-11206732 P114 ABCC11 p.R338H 1.43 16:48249193-48249194 P114 FAT1 p.D3281Y 1.29 4:187532551-187532552 P114 ROS1 p.N2008S 1.21 6:117638417-117638418 P114 MLL3 p.R3079* 0.92 7:151873302-151873303 P114 APC p.A2108V 0.68 5:112177613-112177614 P115 NOTCH3 p.V1697M 0.47 19:15281166-15281167 P115 HDAC4 p.A165V 0.45 2:240085615-240085616 P116 KRAS p.G13D 15.87 12:25398280-25398281 P116 APC p.E1397Vfs*16 14.50 5:112175477-112175484 P116 MITF p.R64H 12.39 3:69928373-69928374 P116 TP53 p.R213* 12.20 17:7578211-7578212 P116 CSF1R p.R256C 12.15 5:149456961-149456962 P116 FBXW7 p.S582L 11.70 4:153245445-153245446 P116 GNAS p.C360Y 10.73 20:57485774-57485775 P116 ABCC11 p.R1241H 9.10 16:48204854-48204855

P116 FBXW7 NA 8.55 4:153258952-153258953 P116 DNAJC11 p.E95K 8.35 1:6727863-6727864 P117 BRAF p.V600E 46.79 7:140453135-140453136 P117 OR6F1 p.V260I 41.58 1:247875279-247875280 P117 TP53 p.P152Afs*14 39.45 17:7578463-7578476 P117 NOTCH1 p.D352Y 35.62 9:139413087-139413088 P117 CDK12 p.R1473W 33.93 17:37687512-37687513 P117 RNF43 p.D144Gfs*6 31.55 17:56440906-56440906 P117 FNDC4 p.G40V 9.94 2:27717427-27717428 P117 APC p.R24Q 1.15 5:112090657-112090658 P117 CBL p.G425V 1.08 11:119149265-119149266 P117 SMARCA4 p.R1192C 0.77 19:11143992-11143993 P117 FAT1 p.T1585M 0.39 4:187549363-187549364 P117 MLL4 p.R698H 0.24 19:36212341-36212342 P117 SMO p.F460L 0.23 7:128849149-128849150 P118 DNMT3A p.Q417* 0.76 2:25467058-25467059 P119 APC p.Q1406* 43.44 5:112175506-112175507 P119 TP53 p.R175H 39.91 17:7578405-7578406 P119 KRAS p.G12D 25.30 12:25398283-25398284 P119 KDR p.G152R 4.89 4:55981482-55981483 P119 PALB2 p.H1061L 0.57 16:23625343-23625344 P120 HDAC1 p.L298V 63.40 1:32796421-32796422 P120 TP53 p.R213* 62.50 17:7578211-7578212 P120 KRAS p.G13D 57.50 12:25398280-25398281 P120 CTNNB1 p.L640P 48.70 3:41277954-41277955 P120 JAK1 p.Y654C 30.20 1:65312357-65312358 P120 MAP2 NA 22.20 2:210564998-210564999 P120 FGFR3 p.P167S 0.51 4:1803146-1803147 P120 SPTA1 p.E862D 0.50 1:158631077-158631078 P121 TP53 p.H168Qfs*2 12.76 17:7578425-7578426 P121 PIK3R2 p.E526* 12.22 19:18277955-18277956 P121 MAP2K2 p.E287[2>1] 6.60 19:4099252-4099255 P121 NOTCH3 p.R1036Q 5.60 19:15291526-15291527 P121 ST18 p.K902N 5.54 8:53038660-53038661 P121 PDGFRB p.R604H 0.79 5:149504390-149504391 P121 TMEM247 p.P73S 0.66 2:46707642-46707643 P122 TP53 p.R273H 48.01 17:7577119-7577120 P122 APC p.R216Hfs*5 30.89 5:112116593-112116593 P122 FAT1 p.S1336P 2.31 4:187557355-187557356 P122 CHEK1 p.G281C 1.33 11:125513712-125513713 P122 TGFBR1 p.D333H 0.88 9:101907036-101907037 P123 OR4C6 p.T243K 0.97 11:55433369-55433370 P123 POM121L12 p.P89L 0.83 7:53103629-53103630 P123 APC p.N1455Ifs*18 0.79 5:112175654-112175657 P123 TP53 p.I195T 0.76 17:7578264-7578265 P123 APC p.R876* 0.58 5:112173916-112173917 P123 KRAS p.G12D 0.54 12:25398283-25398284 P124 THSD7A p.R1125Q 1.74 7:11464331-11464332 P124 APC p.R232* 1.03 5:112128190-112128191 P124 KRAS p.G12S 0.59 12:25398284-25398285 P125 APC p.E1379* 36.00 5:112175425-112175426 P125 TP53 NA 26.30 17:7576851-7576852 P125 MAP3K1 p.N1069D 19.60 5:56178231-56178232 P125 EGFR p.S464L 5.81 7:55227923-55227924

P125 EGFR p.G465R 3.50 7:55227925-55227926 P125 EGFR p.S442R 3.08 7:55227858-55227859 P125 EGFR p.V441D 3.00 7:55227854-55227855 P125 EGFR p.G465E 1.67 7:55227926-55227927 P125 EGFR p.K467T 1.05 7:55227932-55227933 P125 EGFR p.G465R 0.95 7:55227925-55227926 P125 EGFR p.I491K 0.78 7:55228004-55228005 P125 PIK3CA p.H1047R 0.51 3:178952084-178952085 P126 APC p.S1411Rfs*4 1.90 5:112175523-112175524 P126 TP53 p.T231Pfs*16 1.70 17:7577590-7577591 P126 EPHA3 p.V506I 1.59 3:89448551-89448552 P126 KRAS p.Q61L 1.26 12:25380275-25380276 P126 ENPP2 p.S447F 0.80 8:120602767-120602768 P126 POM121L12 p.S183N 0.53 7:53103911-53103912 P127 KRAS p.G12D 40.40 12:25398283-25398284 P127 FBXW7 p.S195N 35.70 4:153271193-153271194 P127 APC p.R1273* 22.20 5:112175107-112175108 P127 ALK p.V1545I 21.80 2:29416319-29416320 P127 MITF p.K206N 19.80 3:70001020-70001021 P127 APC p.T1438Hfs*35 17.02 5:112175599-112175600 P127 ERBB4 p.D1018A 3.64 2:212285247-212285248 P128 TP53 p.C229Yfs*10 45.65 17:7577593-7577595 P128 RNF43 p.W165Sfs*9 40.88 17:56440724-56440724 P128 INHBA p.Q287P 5.85 7:41729668-41729669 P128 ERBB3 p.L436V 1.64 12:56487159-56487160 P128 CDK12 p.R890C 1.32 17:37667782-37667783 P129 BRCA1 p.S1271R 0.40 17:41243734-41243735 P130 KRAS p.G13D 0.35 12:25398280-25398281 P130 TP53 p.R273H 0.30 17:7577119-7577120 P130 CDK13 p.S1104G 0.04 7:40132457-40132458 P130 NF1 p.A966T 0.03 17:29556897-29556898 P130 FGFR3 p.R359* 0.03 4:1804784-1804785 P130 XRCC1 p.S266L 0.03 19:44056974-44056975 P131 KRAS p.G13D 31.10 12:25398280-25398281 P131 PIK3CA p.G118D 22.78 3:178917477-178917478 P131 FBXW7 p.S582L 21.42 4:153245445-153245446 P131 TP53 p.Q331* 19.01 17:7576854-7576855 P131 APC p.P1453* 18.81 5:112175646-112175654 P131 TP53 p.R213Q 18.24 17:7578210-7578211 P131 BAX p.R37* 16.29 19:49458965-49458966 P131 FBXW7 p.W425C 15.98 4:153249502-153249503 P131 APC p.R283* 15.34 5:112151203-112151204 P131 MAP2K4 p.R274G 2.13 17:12028616-12028617 P131 OR4A15 p.L182R 0.98 11:55135903-55135904 P131 DNMT3A p.Y719C 0.86 2:25457163-25457164 P131 MAP2K4 p.L223F 0.59 17:12013726-12013727 P132 KRAS p.G12V 2.22 12:25398283-25398284 P132 TP53 p.R273C 1.85 17:7577120-7577121 P132 IRS2 p.G65V 0.81 13:110438206-110438207 P132 RET p.S896Y 0.73 10:43615607-43615608 P132 NOTCH4 p.Y752N 0.53 6:32181530-32181531 P133 NOTCH4 p.Y752N 1.67 6:32181530-32181531 P134 PALB2 p.S652I 0.43 16:23641519-23641520 P134 FCGR2B p.T289S 0.40 1:161647274-161647275

P135 MCL1 p.K40del 1.98 1:150551886-150551889 P135 MSH2 p.Q158* 1.84 2:47637337-47637338 P135 ATM p.G2922V 1.42 11:108224585-108224586 P135 SIDT2 p.A604T 1.14 11:117062667-117062668 P135 GNAS p.R202H 1.04 20:57484420-57484421 P135 NOTCH1 p.R2179Q 1.01 9:139391654-139391655 P135 ATR p.R1951* 0.96 3:142215249-142215250 P135 JAK1 p.A449T 0.95 1:65323451-65323452 P135 MSH2 p.L291R 0.93 2:47641486-47641487 P135 PKLR NA 0.89 1:155265226-155265227 P135 JAK1 p.V1000I 0.89 1:65303756-65303757 P135 KRAS p.G12D 0.87 12:25398283-25398284 P135 CCND2 p.A278V 0.84 12:4409137-4409138 P135 PKLR p.P150L 0.72 1:155265285-155265286 P135 FAT1 p.R3957C 0.69 4:187521285-187521286 P135 INPP4B p.V741E 0.65 4:143033748-143033749 P135 FBXW7 p.R222* 0.55 4:153268143-153268144 P135 ATM p.R2993* 0.50 11:108235934-108235935 P136 TP53 p.G302Rfs*8 11.55 17:7577034-7577034 P136 KRAS p.A146V 3.67 12:25378560-25378561 P136 NF1 NA 3.07 17:29665719-29665720 P136 NRAS p.G12V 1.32 1:115258746-115258747 P136 TP53 p.G266E 0.75 17:7577140-7577141 P136 BRCA2 p.I3339V 0.47 13:32972664-32972665 P137 FLT4 p.V148D 0.00 5:180057294-180057295 P138 KRAS p.G12D 1.45 12:25398283-25398284 P138 POM121L12 p.E79K 1.15 7:53103598-53103599 P138 CDH23 p.T1979M 1.04 10:73550056-73550057 P138 ARHGAP40 p.R433C 0.72 20:37270388-37270389 P138 TP53 p.G266V 0.64 17:7577140-7577141 P138 TP53 p.C242F 0.61 17:7577555-7577556 P139 PIK3CB p.S631R 10.01 3:138413628-138413629 P139 APC p.R876* 8.05 5:112173916-112173917 P139 KRAS p.G12V 7.54 12:25398283-25398284 P139 CDKN2A p.R80* 7.42 9:21971119-21971120 P139 PRKAA1 p.E498K 6.53 5:40763112-40763113 P139 ATM p.C532* 6.25 11:108121787-108121788 P139 APC p.T1556Nfs*3 4.85 5:112175951-112175951 P139 BRD2 p.T289S 4.52 6:32944377-32944378 P140 RARA p.T295A 30.17 17:38510628-38510629 P140 PIK3CA p.H1047R 27.41 3:178952084-178952085 P140 ARHGEF1 NA 27.22 19:42396195-42396196 P140 APC p.R2721C 26.57 5:112179451-112179452 P140 NOTCH3 p.R1571Q 26.19 19:15284902-15284903 P140 CHD4 p.D858N 24.34 12:6702336-6702337 P140 MAP3K1 p.Q1425* 24.04 5:56184067-56184068 P140 GNAS p.R231H 23.65 20:57484607-57484608 P140 WDTC1 p.E290Nfs*8 23.46 1:27621107-27621108 P140 BTK p.P190Qfs*9 22.66 X:100617179-100617180 P140 FLT3 p.R773Kfs*14 22.01 13:28597587-28597587 P140 SMARCA4 p.A317V 21.35 19:11098431-11098432 P140 TAF1B p.K63[3>2] 19.53 2:9989570-9989573 P140 NOTCH2 p.G190* 18.72 1:120539802-120539803 P140 GIPR p.C332R 17.73 19:46181232-46181233

P140 SYNJ2 p.P1114Sfs*48 17.65 6:158508008-158508008 P140 JAK3 p.Q228R 14.32 19:17953302-17953303 P140 IRS2 p.N21[8>9] 12.70 13:110438316-110438316 P140 BAX p.E41Rfs*19 10.07 19:49458970-49458971 P140 KRAS p.K117N 8.86 12:25378646-25378647 P140 IGF1R p.D1153Y 8.66 15:99482588-99482589 P140 MSH6 p.F1088Lfs*5 8.47 2:48030639-48030639 P140 FAT1 p.C574R 7.38 4:187629261-187629262 P140 FBXW7 p.S668Vfs*39 6.67 4:153244155-153244156 P140 MSH3 p.K383Rfs*32 5.99 5:79970914-79970915 P140 DDR1 p.L110M 5.29 6:30857117-30857118 P140 HCLS1 p.E394D 5.25 3:121351236-121351237 P140 ABL1 p.A424Hfs*29 4.87 9:133750436-133750437 P140 ATR NA 4.32 3:142215201-142215202 P140 FLOT2 p.T70M 3.89 17:27211255-27211256 P140 CDK13 p.R434H 3.53 7:40027286-40027287 P140 PTCH1 p.S1203Afs*52 2.43 9:98211548-98211549 P140 TRIM51 p.M144Cfs*15 2.05 11:55653609-55653610 P140 MAP2K1 p.G250* 1.82 15:66777381-66777382 P140 FGFR4 p.A447S 1.65 5:176520493-176520494 P140 FAM5C p.A679T 1.62 1:190067413-190067414 P140 TSR2 p.G48Vfs*15 1.60 X:54467178-54467179 P140 MED12 p.G916D 1.34 X:70346879-70346880 P140 CBL p.P201H 1.28 11:119144588-119144589 P140 FLT4 p.A877T 1.22 5:180046682-180046683 P140 MAP3K1 NA 1.19 5:56161653-56161654 P140 IRS2 p.A715T 1.07 13:110436257-110436258 P140 PTPRM p.K932T 1.07 18:8296405-8296406 P140 FBXW7 NA 1.06 4:153333024-153333025 P140 AR p.Y621N 1.04 X:66905943-66905944 P140 GATA3 p.S237Afs*29 1.03 10:8100727-8100728 P140 PIWIL1 p.G337V 0.99 12:130834477-130834478 P140 BRCA2 p.T1302I 0.99 13:32912396-32912397 P140 FLT1 p.L522V 0.97 13:28971192-28971193 P140 PIK3CA p.R88Q 0.94 3:178916875-178916876 P140 NF1 p.I913M 0.93 17:29556371-29556372 P140 PIWIL1 p.G337R 0.92 12:130834476-130834477 P140 BRD3 p.D104Tfs*19 0.87 9:136917468-136917469 P140 MSH6 p.V294A 0.84 2:48026002-48026003 P140 FAT1 p.D2962N 0.81 4:187538349-187538350 P140 PTCH2 p.E106G 0.78 1:45297961-45297962 P140 BRD3 p.Q103L 0.76 9:136917470-136917471 P140 MPL p.R390H 0.73 1:43812465-43812466 P140 NOTCH4 p.R1668C 0.68 6:32165125-32165126 P140 FLT1 p.A519V 0.67 13:28971200-28971201 P140 DDR2 p.M441V 0.63 1:162740118-162740119 P140 ROS1 p.L1937R 0.63 6:117641160-117641161 P140 GLYR1 p.A419V 0.63 16:4862112-4862113 P140 NAV3 p.P359H 0.57 12:78400393-78400394 P140 ESR1 p.R269H 0.53 6:152265352-152265353 P140 PTPN11 p.T507S 0.53 12:112926898-112926899 P140 HGF p.N515K 0.51 7:81336676-81336677 P141 TMEM247 p.Q128E 0.07 2:46707807-46707808 P141 SELP p.A28T 0.04 1:169588378-169588379

P141 EGFR p.L858R 0.03 7:55259514-55259515 P141 BRAF p.F583L 0.02 7:140453185-140453186 P141 TP53 p.R273L 0.02 17:7577119-7577120 P141 DNMT3A p.E697* 0.01 2:25463592-25463593 P142 TP53 p.R213* 27.00 17:7578211-7578212 P142 FLCN p.H429Pfs*27 20.93 17:17119708-17119708 P142 AKT3 p.H284Q 15.30 1:243727117-243727118 P142 APC p.Y1162Ifs*3 14.82 5:112174773-112174774 P142 APC p.E1345* 14.40 5:112175323-112175324 P142 JAK2 p.G1093V 9.94 9:5126432-5126433 P142 C11orf30 p.R62Sfs*10 9.59 11:76164370-76164372 P142 RB1 p.P674L 0.71 13:49033883-49033884 P143 ERBB3 p.L74F 0.50 12:56477671-56477672 P144 APC p.R216* 33.07 5:112128142-112128143 P144 PIK3CA p.P366R 6.81 3:178922327-178922328 P144 FAT1 p.G4147S 1.06 4:187518254-187518255 P144 JAK1 p.T825A 1.05 1:65307214-65307215 P145 FGFR4 p.G388R 0.50 5:176520242-176520243 P146 TP53 p.G266E 5.20 17:7577140-7577141 P146 FAT1 p.M3759L 3.20 4:187524404-187524405 P146 POM121L12 p.W243L 3.10 7:53104091-53104092 P146 FOXL2 p.L195V 2.80 3:138664981-138664982 P146 ROCK1 p.Q740* 0.60 18:18566996-18566997 P146 XRCC1 p.A119V 0.60 19:44058855-44058856 P146 OR2T4 p.I253Sfs*8 0.40 1:248525638-248525639 P147 MTOR p.R403* 0.45 1:11307699-11307700 P148 OR4C6 p.R120H 29.10 11:55433000-55433001 P148 BRAF p.V600E 23.40 7:140453135-140453136 P148 TP53 p.R282W 20.30 17:7577093-7577094 P148 SPINT1 p.E201K 11.10 15:41145446-41145447 P148 MLL3 p.P4749T 10.60 7:151841895-151841896 P148 CHEK2 p.K325R 9.89 22:29095859-29095860 P148 OR4A15 p.L91Sfs*22 5.06 11:55135623-55135623 P149 KEAP1 p.V271M 0.39 19:10602766-10602767 P150 DNMT3A NA 0.62 2:25470028-25470029 P151 APC p.S1344Ffs*10 35.30 5:112175319-112175319 P151 PIK3CA p.H1047R 35.10 3:178952084-178952085 P151 TP53 p.H179R 22.90 17:7578393-7578394 P151 CSF1R p.D806N 18.00 5:149435807-149435808 P151 KRAS p.G12D 12.60 12:25398283-25398284 P151 HDAC4 p.R1029C 5.10 2:239975285-239975286 P152 GNAS p.A270V 10.57 20:57429128-57429129 P152 APC p.Q1429* 10.49 5:112175575-112175576 P152 SETD2 p.K2123Sfs*24 10.02 3:47098907-47098908 P152 KRAS p.Q61L 9.93 12:25380275-25380276 P152 PIK3CA p.E545K 7.01 3:178936090-178936091 P152 OR4A15 p.L4Q 4.17 11:55135369-55135370 P152 APC p.R283* 3.78 5:112151203-112151204 P152 TP53 p.S241F 1.18 17:7577558-7577559 P152 ARAF p.T97A 0.88 X:47424283-47424284 pHGVS, amino acid change; M%, mutant allele frequency; NA, mutations that lead no structural change of encoded protein.

Table S3. Relationship between susceptive mutations and targeted drugs

Gene cHGVS pHGVS Drug (Level)

AKT1 c.49G>A p.E17K MK2206 (3D), Ipatasertib (3D), AZD5363

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), AKT2 Gain Gain MK2206 (3D)

ATM c.2413C>T p.R805* Olaparib (2D), AZD6738 (3D)

ATM c.1596C>A p.C532* Olaparib (2D), AZD6738 (3D)

ATM c.8977C>T p.R2993* Olaparib (2D), AZD6738 (3D)

ATM c.179T[5>4] p.F61Lfs*15 Olaparib (2D), AZD6738 (3D)

ATM c.7166C>G p.S2389* Olaparib (2D), AZD6738 (3D)

ATM c.2251-2A>G NA Olaparib (2D), AZD6738 (3D)

ATM c.5692C>T p.R1898* Olaparib (2D), AZD6738 (3D)

AURKA Gain Gain Rucaparib (2D), Alisertib (3D)

BRAF c.1799T>A p.V600E Dabrafenib (2D), Trametinib (2D)

BRAF c.1781A>G p.D594G Sorafenib (2D), Trametinib (2D), Dabrafenib (2D)

BRCA1 c.607G>T p.E203* Olaparib (2D), Rucaparib (2D), Niraparib (2D)

BRCA2 c.4552G>T p.E1518* Olaparib (2D), Rucaparib (2D), Niraparib (2D)

BRCA2 c.6952C>T p.R2318* Olaparib (2D), Rucaparib (2D), Niraparib (2D)

BRCA2 c.1202C>G p.S401* Olaparib (2D), Rucaparib (2D), Niraparib (2D)

BRCA2 c.317-2A>C NA Olaparib (2D), Rucaparib (2D), Niraparib (2D)

BRCA2 c.8009C>T p.S2670L Olaparib (2D), Rucaparib (2D), Niraparib (2D)

BRCA2 c.6502G>T p.G2168* Olaparib (2D), Rucaparib (2D), Niraparib (2D)

CCND1 Gain Gain Palbociclib (2D), Ribociclib (2D), Abemaciclib (3D)

CCND2 Gain Gain Palbociclib (2D), Ribociclib (2D), Abemaciclib (3D)

CDKN2A c.238C>T p.R80* Palbociclib (2D), Ribociclib (2D), Abemaciclib (3D)

CDKN2A c.247C>T p.H83Y Palbociclib (2D), Ribociclib (2D), Abemaciclib (3D)

CTNNB1 c.121A>G p.T41A Celecoxib (2D)

CTNNB1 c.110C>T p.S37F Celecoxib (2D)

EGFR c.1391C>T p.S464L MM-151 (3D)

EGFR c.1393G>A p.G465R MM-151 (3D) Sym004 (3D)

EGFR c.1393G>C p.G465R MM-151 (3D) Sym004 (3D)

EGFR c.1400A>C p.K467T MM-151 (3D) Sym004 (3D)

Gefitinib (2D), Erlotinib (2D), Afatinib (2D), Icotinib EGFR c.2573T>G p.L858R (2D), Osimertinib (2D), Dacomitinib (3D), AZD3759 (3D)

Trastuzumab (2D), Lapatinib (2D), Afatinib (2D), T- ERBB2 c.2327G>T p.G776V DM1 (2D), Neratinib (3D)

ERBB2 c.2264T>C p.L755S Afatinib (2D), Neratinib (3D), T-DM1 (2D)

Afatinib (2D), Neratinib (3D), Trastuzumab (2D), ERBB2 c.2524G>A p.V842I Lapatinib (2D), T-DM1 (2D)

ERBB2 Gain Gain Trastuzumab (2D)

ERBB3 c.695C>T p.A232V Trastuzumab (2D), Pertuzumab (2D), Lapatinib (2D),

Afatinib (2D)

Trastuzumab (2D), Pertuzumab (2D), Lapatinib (2D), ERBB3 c.310G>A p.V104M Afatinib (2D)

FBXW7 c.3G>T NA Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FBXW7 c.861+1G>A NA Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FBXW7 c.1393C>T p.R465C Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FBXW7 c.1394G>A p.R465H Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FBXW7 c.1996G[6>5] p.S668Vfs*39 Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FBXW7 c.664C>T p.R222* Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FBXW7 c.670C>T p.R224* Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FBXW7 c.79C>T p.Q27* Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FBXW7 c.1436G>A p.R479Q Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FBXW7 c.1479T>A p.C493* Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FBXW7 c.584+2T>C NA Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FBXW7 Loss Loss Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

Ponatinib (2D), Dovitinib (3D), BGJ398 (3D), FGFR1 Gain Gain AZD4547 (3D)

Pazopanib (2D), Ponatinib (2D), Dovitinib (3D), FGFR2 Gain Gain BGJ398 (3D), AZD4547 (3D)

Pazopanib (2D), Ponatinib (2D), Dovitinib (3D), FGFR3 c.1948A>G p.K650E BGJ398 (3D), AZD4547 (3D)

Pazopanib (2D), Ponatinib (2D), Dovitinib (3D), FGFR3 c.1144G>A p.G382R BGJ398 (3D), AZD4547 (3D)

FLCN c.1278C[8>9] p.H429Pfs*27 Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FLCN c.640G>T p.G214* Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FLCN c.506G>A p.W169* Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FLCN Loss Loss Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

FLT3 Gain Gain Sorafenib (2C), Sunitinib (2D)

INPP4B c.853G>T p.E285* Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

JAK2 c.1614C>G p.H538Q Ruxolitinib (2D), Tofacitinib (2D), Momelotinib (3D)

JAK2 Gain Gain Ruxolitinib (2D), Tofacitinib (2D), Momelotinib (3D)

KRAS c.35G>A p.G12D Selumetinib (3B), MEK162 (3D), PD0325901 (3D)

KRAS c.34G>A p.G12S Selumetinib (3B), MEK162 (3D), PD0325901 (3D)

MET Gain Gain Crizotinib (2D), Cabozantinib (2D), Tivantinib (3D)

MTOR c.6644C>A p.S2215Y Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

MTOR c.5395G>A p.E1799K Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

NF1 c.7285C>T p.R2429* Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

NF1 c.6757-2A>T NA Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

NF1 c.4033A>T p.K1345* Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

NF2 c.739dupG p.E247Gfs*14 Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

c.1208_1212dupCAG Everolimus (2D), Sirolimus (2D), Temsirolimus (2D) NF2 p.A405Qfs*23 AG

NF2 Loss Loss Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

NTRK1 Gain Gain Crizotinib (2D), Entrectinib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.1624G>A p.E542K Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.1633G>A p.E545K Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.3062A>G p.Y1021C Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.3140A>G p.H1047R Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.1636C>A p.Q546K Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.353G>A p.G118D Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.263G>A p.R88Q Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.1616C>G p.P539R Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.3145G>A p.G1049S Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.113G>A p.R38H Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.241G>A p.E81K Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.1625A>T p.E542V Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.3132T>G p.N1044K Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.1637A>G p.Q546R Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

PIK3CA c.1634A>C p.E545A Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), 33

Dactolisib (3D), Buparlisib (3D), Alpelisib (3D) Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA c.1635G>C p.E545D Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3CA Gain Gain Dactolisib (3D), Buparlisib (3D), Alpelisib (3D), Taselisib (3D)

PIK3CB Gain Gain Dactolisib (3D)

c.1738_1745+1delTA Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3R1 NA CTTGATG PD0325901 (3D), MK2206 (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3R1 c.871G>T p.E291* MK2206 (3D), PD0325901 (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PIK3R1 Loss Loss MK2206 (3D), PD0325901 (3D)

PTCH1 c.3601C[6>5] p.S1203Afs*52 Vismodegib (2D), Sonidegib (2D)

PTCH1 c.3915C[7>6] p.R1308Efs*64 Vismodegib (2D), Sonidegib (2D)

PTCH1 c.3883C[3>2] p.G1296Dfs*76 Vismodegib (2D), Sonidegib (2D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PTEN c.877G>T p.G293* Dactolisib (3D), Buparlisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PTEN c.389G>A p.R130Q Dactolisib (3D), Buparlisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PTEN c.810dupG p.F271Vfs*27 Dactolisib (3D), Buparlisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PTEN c.795A[6>5] p.K267Rfs*9 Dactolisib (3D), Buparlisib (3D)

Everolimus (2D), Sirolimus (2D), Temsirolimus (2D), PTEN Loss Loss Dactolisib (3D), Buparlisib (3D)

Sorafenib (2D), Trametinib (2D), Selumetinib (3B), RAF1 c.770C>T p.S257L MEK162 (3D)

RET Fusion Fusion Cabozantinib (2D), Lenvatinib (2D), Vandetanib (2D)

SMARCA4 Loss Loss Vorinostat (2D)

SMARCB1 c.907TdelT p.L303Wfs*17 EPZ-6438 (3D)

SMARCB1 Loss Loss EPZ-6438 (3D)

STK11 c.597+1G>C NA Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

STK11 c.837C[6>5] p.P281Rfs*6 Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

TSC1 c.1498C>T p.R500* Everolimus (2D), Sirolimus (2D), Temsirolimus (2D)

TSC1 c.2080C>T p.Q694* Everolimus (2D), Sirolimus (2D), Temsirolimus (2D) cHGVS, nucleotide change; pHGVS, amino acid change.

Table S4. Comparison of the mutational profiles of matched blood and tumor tissue samples

Patient Gene pHGVS Tissue M(%) Blood M(%) P033 APC p.Q1447* 43.40 38.20 P033 CTNNB1 NA 42.50 37.80 P033 KDR p.A1127D 43.20 36.70 P033 KRAS p.Q61R 44.20 37.60 P033 NRAS p.G13D 39.70 36.30 P033 PIK3CA p.E545K 40.80 37.70 P033 TP53 p.R282W 79.60 63.80 P033 DNMT3A p.I32S NA 0.58 P033 EPHA5 p.E631D NA 0.93 P033 EPHA5 p.E632* NA 0.79 P033 EZH2 p.N673K NA 0.82 P033 GNAS p.P141S NA 0.70 P033 KDR p.N175T NA 5.97 P033 OR5L2 p.I228L NA 0.53 P035 DDR2 p.K763T 23.02 1.03 P035 EPHA3 p.N79T 29.84 1.08 P035 KRAS p.G12V 66.99 1.03 P035 MLL p.D433Y 69.33 1.42 P035 NTRK3 p.K564Rfs*8 24.96 NA P035 NTRK3 p.T563N 25.84 NA P035 OR4C6 p.V31A 64.41 0.82 P035 TP53 p.V172F 88.90 0.78 P035 TRIM58 p.F329L 32.02 0.83 P035 MYD88 p.R2* NA 0.57 P035 ROS1 p.E1580K NA 0.55 P039 APC p.E893* 42.13 1.64 P039 APC p.S1465Wfs*3 33.39 2.02 P039 FGFR3 p.G54R 28.31 0.97 P039 FLT1 p.R1305H 1.86 NA P039 KRAS p.G12D 55.79 1.30 P039 TP53 p.P151R 80.51 1.39 P039 TERT NA NA 0.65 P042 KRAS p.A146T 37.53 38.94 P042 PTPRD p.V1186A 9.24 NA P042 TP53 NA 74.74 46.03 P042 HIST1H3B p.Q126P NA 28.81 P042 KEAP1 p.C273R NA 16.30 P042 APC p.R1450* NA 0.76 P042 PALB2 p.N1003D NA 0.46 P059 APC p.W421* 14.60 47.00 P059 TP53 p.E286Sfs*56 18.50 45.50 P059 NF2 p.A405Qfs*23 NA 35.20 P066 FBXW7 p.R465C 22.27 10.15 P066 KRAS p.G13D 37.32 22.59 P066 MITF p.R214* 26.54 9.69 P066 PRKAA1 p.R461* 1.21 NA P066 TP53 p.G245S 47.81 24.49 P066 MLH3 p.P1402Q NA 3.01 P066 SETD2 p.I2411T NA 5.87 P067 APC p.S770* 20.58 5.86 P067 KRAS p.G13C 21.05 8.81

P067 MTOR p.W1521* 1.15 NA P076 ALK p.S737L 1.70 6.80 P076 BRAF p.V600E 1.70 6.10 P076 TP53 p.I195T 2.00 9.50 P076 PIK3CA p.E545D NA 4.10 P076 PTCH2 p.H783L NA 0.30 P107 ALK p.A942T 7.34 NA P107 APC p.E1309Dfs*4 39.12 11.43 P107 FBXW7 p.D560Y 23.17 2.93 P107 FBXW7 p.R224* 23.78 11.69 P107 KRAS p.G12V 29.06 11.41 P107 PIK3R1 p.G627R 24.92 3.85 P107 TP53 p.R267G 21.99 13.26 P138 ARHGAP40 p.R433C 10.83 0.72 P138 CDH23 p.T1979M 14.04 1.04 P138 KRAS p.G12D 13.47 1.45 P138 POM121L12 p.E79K 10.66 1.15 P138 TP53 p.C242F 14.00 0.61 P138 TP53 p.G266V 7.39 0.64 P139 APC p.R876* 10.97 8.05 P139 APC p.T1556Nfs*3 9.09 4.85 P139 ATM p.C532* 13.73 6.25 P139 BRD2 p.T289S 7.52 4.52 P139 CDKN2A p.R80* 35.59 7.42 P139 KRAS p.G12V 21.91 7.54 P139 PIK3CB p.S631R 27.82 10.01 P139 PRKAA1 p.E498K 11.80 6.53 M(%), mutant allele frequency; NA, mutations that lead no structural change of encoded protein.