(A) TCGA-LUAD, (B) TCGA-LUSC, (C) Database from Rizvi H, Et Al
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Figure S1. The correlations of TMB value between panel sequencing and WES in published databases. (A) TCGA-LUAD, (B) TCGA-LUSC, (C) Database from Rizvi H, et al. J Clin Oncol, 2018;36. Abbreviations: TMB, tumor mutational burden; TCGA, The Cancer Genome Atlas; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; WES, wholeexome sequencing A B C 1 / 3 Figure S2. The comparison of multi-region tTMB among different NSCLC subtypes. Abbreviations: TMB, tumor mutational burden; tTMB, tissue TMB 2 / 3 Figure S3. The comparisons and overlaps of tumor-derived mutational profiles among tumor tissues in each region and the corresponding ctDNA. The P0XX was the patient No. shown at the top. Each tumor region (T1, T2, T3…) with plasma (P) were arranged in the x axis. ctDNA was isolated from plasma (more details in Supplementary Methods). Right y axis displayed tumor-derived mutational profiles in detail. The detected mutations were shown in red, while undetected cases were shown in gray. 3 / 3 P001 P004 P005 P006 P007 P009 P015 P018 KRAS.p.G12C ATG9B.p.R298C MORC1.p.G97V MLH1.p.L658V EGFR.p.L747_E749del SPTA1.p.S444C VAV1.p.R548W TP53.p.Y163C BAX.p.E41G CSMD3.p.H1455Y FAT1.p.R4481L CHI3L1.p.G37S DDR2.p.R478C APC.p.E2184K EPOR.p.R45P PTCH2.p.E854K TENM3.p.S44I EGFR.p.L858R U2AF1.p.S34F STK11.p.I238F MAEL.c.703.1G.C PIK3CA.p.R108H MSH6.p.S1340C EGFR.p.E746_A750del TSC1.p.R779. FLT1.p.K37E XRCC1.p.E455Q TP53.c.443.2A.C EGFR.p.A750P PPEF1.p.R348Q NTRK3.p.D208E TP53.p.Q105_S110delinsP DNMT3A.p.F563I NF1.p.A1228T CDK13.p.K852Nfs.23 POLR3B.c.1102.3_1102.2delTA COL6A6.p.P1542S MYD88.p.L265P FLT4.p.A601V TERT.c..58.u3403C.A ACIN1.p.K1047N ERBB2.p.G746delinsVC PRKCD.p.G210V EPHA3.p.T519M NOTCH1.p.Q2361. ANKRD27.p.G744V EGFR.p.L858R FAT1.p.V4575E PRSS1.p.E32D RB1.p.A433Lfs.24 ARHGEF1.p.S25F TP53.p.V134A TP53.p.H193Y EZH2.p.S40Ifs.17 KDR.p.S410R P P T1 T2 T3 INHBA.p.E154K EGFR.gain T1 T2 T3 T4 OR5L2.p.C260. NTRK2.p.R413I ERBB4.p.R484K P T1 T2 T3 T4 T5 T6 P P019 P026 EPHA5.p.F214C MLL3.p.Q560Sfs.53 T1 T2 T3 T4 KDR.gain TP53.p.M345Nfs.39 LCT.p.F314Lfs.7 MTTP.p.S383I EPHA5.p.S992I MSH3.p.A51.12.9. KIT.gain PDGFRA.gain TP53.p.R234L P003 MAP2K1.p.L375P P POM121L12.p.D11E BRAF.c.2128.2_2128delAGA T1 T2 T3 P002 P FMN2.p.E1640K T1 T2 T3 T4 CTNNB1.p.S37F CCNE1.gain KEAP1.p.E244K TP53.p.W52. ATR.p.Q416E EGFR p.E746_A750del EGFR.p.E746_A750del MLL4.p.D1842E P EGFR.p.L858R P T1 T2 T3 T4 T1 T2 T3 T4 CTNNB1.p.Q72E P T1 T2 T3 T4 T5 T6 T7 NOTCH2.p.E301K ALK.p.P496S P T1 T2 T3 T4 T5 T6 P RB1.c.1696.1G.C T1 T2 T3 T4 T5 P T1 T2 T3 T4 T5 T6 T7 T8 P008 P016 P017 P020 P021 P030 P025 FBXW7.p.R473G TRIM58.p.D321E GNAS.p.S110C MTOR.p.F191Lfs.20 SLC25A30.p.W266Gfs.5 OR4A15.p.V222I MTOR.p.N1264S NAV3.p.D414V CNTNAP5.p.Q909L AR.p.Q71R SMARCA4.p.E665_E666delinsD. MET.p.Y989N IGSF9.c.1198.1G.A BRAF.p.G469V ROS1.p.L567M DOCK3.p.L1854H MYD88.p.L265P AURKA.p.K143E SEPT12.p.R266Q FAM5C.p.P690T NOTCH2.p.R1578C ABCC11.p.C609F MTOR.p.N2494Ifs.74 TP53.p.K100N NOTCH2.p.L1844V ROS1.p.R2039P FGFR1.p.R448W MYC.p.K158E KRAS.p.G12V PTPRD.p.T799A NF1.p.V350G GNAQ.c.736.2_736.1insA OR4A15.p.L83M CDH18.p.G664. MLL.p.P36L C1S.p.N233Tfs.6 STK11.c.456_464.6del CNTN5.p.T176N MET.c.2941.1G.T MLH1.p.Q149Rfs.11 RET.p.G727. CRYBG3.p.K2356Rfs.3 MLL4.p.C1325F TMEM247.p.Q152_Q153ins ERBB4.p.P309Lfs.7 KRAS.p.G12D FGFR4.p.R196L TNN.p.P680Q TP53.p.H76Ifs.8 AR.p.I304V FAT1.p.D1204V ABL1.p.T993A NAV3.p.A503P EGFR.p.L858R FLT3.p.Y874C CDH23.p.I743F GNAS.p.R524S FBXW7.p.W486Gfs.12 SMARCA4.p.A503S CCNE1.p.R385M PDGFRB.p.P725R PTPRD.p.D848N RICTOR.p.I188F CDK13.p.R1317Efs.39 ALK.p.A195V RET.p.E713D SLCO5A1.p.V677L TSC1.c.2623.2_2623.1insA MED12.p.Q2146.5.4. ROS1.p.G666Vfs.16 CD274.p.L214. ALK.p.M1478T AR.p.G260V MLL3.p.A221P EML4.ALK FOXL2.p.P285Rfs.71 TP53.p.R209L ROS1.p.V1175L EPHA5.p.I850T COL25A1.p.G382Dfs.48 TP53.p.N272Kfs.33 TP53.p.R119L OR4C6.p.M279I DNMT3A.p.G332R FGFR3.p.Y673Hfs.5 CTNNA2.p.R125Q MTOR.p.E742K POM121L12.p.R49P GNAS.p.S455Y OR4C6.p.L280V GPR114.p.M34T ERBB4.p.G1293V EGFR.gain TP53.p.R234S GAB2.p.Q562Sfs.172 OR4A15.p.P86H FAT1.p.P381R MLH1.p.G517R NOTCH1.p.E1583Sfs.33 OR2T4.p.I229F EPHA5.p.P561L GFRAL.p.H206Q MITF.p.A285Pfs.12 CDK4.gain EPHA5.p.D180Y PTPRD.p.V834L MLL4.p.V169L P P P T1 T2 T3 T4 OR6F1.p.D269Y THBS2.p.C835Y T5 T6 T7 T2 T3 T4 T5 T6 T1 T1 T2 T3 T4 T5 CRKL.p.P231S EZH2.p.T244M P ANKRD36B.p.I480M T1 T2 T3 T4 T5 T6 T7 T8 AR.p.Q74R FAT1.c.3629_3642.5del SMARCA4.p.Q459_K461del TERT.c..58.u2712G.T P T1 T2 T3 T4 T5 T6 FGFR2.p.C809F P ERBB2.p.E580G T1 T2 T3 T4 T5 T6 T7 T8 AXL.p.E281G TP53.p.S201C P T2 T5 T1 T6 T3 T4 P022 P027 P028 P029 P033 P034 P037 MED12.p.S2163F HDAC4.p.K1071N MLL4.p.D131H ROS1.p.S852R APC.p.Q1469. NOTCH4.p.G1081C EMID2.p.L96Q EPHA2.p.V442A GNAQ.p.G46W CCND2.p.L20M SMO.p.E779K TP53.p.C199F TSC1.p.A566V MED12.p.G1293A COL6A5.p.M1319V NOTCH2.p.P2463S HGF.p.F99L NOTCH2.p.G523V ENPP2.p.R446. OR2T4.p.A30D PTPRD.p.D991H ATM.p.A2346G EGFR.p.E45K TRPC5.p.M86I CTNNB1.p.I507. TMEM247.p.G86. HDAC4.p.E645D NF1.p.Q83. MLL3.p.H4429L NOTCH4.c.2022.1G.T AXL.p.V406L CCND3.p.A266V MTTP.p.S385C BRD2.p.K127N BRCA1.p.K1233. NF1.p.I177T CDH23.p.G252C ROCK1.p.V1127G ESR1.p.D332Y MITF.p.Q30. TERT.c..58.u1680C.A SMARCA4.p.K455M GPATCH2.p.P383L HECTD4.p.G4219V C11orf30.p.Q728. TP53.p.A99V TMTC4.c.1586.1G.A FUNDC1.p.E130Q PDGFRA.p.P698Q FGFR4.p.V740L CNOT3.p.K544N FAT1.p.P1877Lfs.20 RICTOR.p.A3V KIAA0319.p.D909Y GNAS.p.S532C DNMT3A.p.G298W NF1.p.A2028S FGFR3.p.S612F CSMD3.p.H775N MLL3.p.D3152N CCNE1.p.R27H SETD2.p.D631N FAM5C.p.Q471K MPL.p.R43. PIK3R2.p.G363C MAP3K1.p.K953R TESC.p.R59L SETD2.p.E850K GATA3.c.1050.2T.A CHEK2.p.L106V EPHA3.c.1307.1G.T FASTK.p.K530N EPHA2.p.N71Y NTRK3.p.C166F PALB2.p.S631P DDR2.p.R746L MAP3K1.p.P981S MLL4.p.P1124R CD97.p.K156Rfs.6 TP53.p.G227. EPOR.p.S176F EPHA3.p.P291Q NF2.c.1575.1G.C OR4A15.p.C217F XRCC1.p.I232M MLL3.p.G3106R CNOT3.p.P269Afs.15 SMARCA4.p.Y439. VEGFA.p.G117V FGFR1.p.F114V KRAS.p.G12V HDAC4.p.S735R TGFBR1.p.G301R KEAP1.p.D526Y MDM4.p.R149G HCN1.p.R593Q KEAP1.p.R601L SMARCA4.p.E1242G RB1.p.T601Ifs.7 TP53.p.R234H FAT1.p.V2936. MLL4.p.D168H NOTCH4.p.P445H TP53.p.R209L HCLS1.p.E394D FBXW7.p.W244. RPS6KB1.p.A348T BRCA2.p.E2599K KRAS.p.G12V ERBB2.p.R816L PTEN.p.V166G FGFR3.p.S249F ERBB4.p.P572L ERBB2.c.2086.1G.A CDH23.p.F895L MLL3.p.Q1211. CDK12.p.S256W OR2T4.p.Y136. ABL2.p.E398K ARHGAP40.p.P447T NF1.p.L1183V FAT1.p.A3666T FLT1.p.S530P NOTCH2.p.H2041R KEAP1.p.A40S DUOX1.p.R1219Q MLL3.p.S1228. DDR2.p.R128H MAP2K1.p.R201C NOTCH1.p.R2327W TP53.p.C203F RB1.p.Q257. STAT3.p.E625D P WAS.c.1453.1G.T ERBB4.p.G565C T1 T2 T3 T4 T5 T6 T7 T8 ELAVL3.p.A18Rfs.34 HDAC1.p.G280A OR2T4.p.L58I NOTCH2.p.E494Q ROBO3.p.S307I OR4C6.p.C205F C1S.p.Q318H FGFR1.p.E803. ABCC11.p.E1169K ERBB3.p.Q239E TCP11.p.Q43H DDR2.p.P384H P OR6F1.p.T160I EPHA3.p.Q139. CCND1.gain T1 T2 T3 T4 T5 T6 ABCC11.p.L958Q ATM.p.R250Q CCND1.p.E76Q ALK.p.E152. KCNH6.p.D673H DNMT3A.p.G800R RB1.p.T601Ifs.7.1 HRAS.c..53.1G.T BRCA2.p.D1990H P MCL1.p.G59_G62del OR5L2.p.L220. MLL3.p.R4478P T1 T2 T3 T4 T5 T6 T7 T8 FAT1.p.M1533I ALK.p.E717K NOTCH2.p.E2143Q CDKN2A.p.G101V PRKAA1.p.S5R MLL.p.D649H SETD2.p.R484S P FGFR2.p.C740G OR5L2.p.T57N RAF1.p.E503Q T1 T2 T3 T4 CDK12.gain HGF.p.V64. CDH23.c.754.2A.T EPHA3.p.R330K ERBB2.gain FOXL2.p.Q344. CDK13.p.S1066. EGFR.p.Y1110C NF1.p.D1849N P T1 T3 T4 T5 T6 PDGFRA.p.P6S T2 T7 T8 KDR.p.Q72. CD74.ROS1 P030 P031 P035 P036 TP53.p.Q38.