EGAGenomicsDeokhoon Kimhttps://ega-archive.org/dacs/EGAC00001000329EGAEGA DAC EGAC00001000329EGAcoonya@gmail.com<h4>Unlabelled</h4>Hepatic resection is the most curative treatment option for early-stage hepatocellular carcinoma, but is associated with a high recurrence rate, which exceeds 50% at 5 years after surgery. Understanding the genetic basis of hepatocellular carcinoma at surgically curable stages may enable the identification of new molecular biomarkers that accurately identify patients in need of additional early therapeutic interventions. Whole exome sequencing and copy number analysis was performed on 231 hepatocellular carcinomas (72% with hepatitis B viral infection) that were classified as early-stage hepatocellular carcinomas, candidates for surgical resection. Recurrent mutations were validated by Sanger sequencing. Unsupervised genomic analyses identified an association between specific genetic aberrations and postoperative clinical outcomes. Recurrent somatic mutations were identified in nine genes, including TP53, CTNNB1, AXIN1, RPS6KA3, and RB1. Recurrent homozygous deletions in FAM123A, RB1, and CDKN2A, and high-copy amplifications in MYC, RSPO2, CCND1, and FGF19 were detected. Pathway analyses of these genes revealed aberrations in the p53, Wnt, PIK3/Ras, cell cycle, and chromatin remodeling pathways. RB1 mutations were significantly associated with cancer-specific and recurrence-free survival after resection (multivariate P = 0.038 and P = 0.012, respectively). FGF19 amplifications, known to activate Wnt signaling, were mutually exclusive with CTNNB1 and AXIN1 mutations, and significantly associated with cirrhosis (P = 0.017).<h4>Conclusion</h4>RB1 mutations can be used as a prognostic molecular biomarker for resectable hepatocellular carcinoma. Further study is required to investigate the potential role of FGF19 amplification in driving hepatocarcinogenesis in patients with liver cirrhosis and to investigate the potential of anti-FGF19 treatment in these patients.Genomic portrait of resectable hepatocellular carcinomas: implications of RB1 and FGF19 aberrations for patient stratification.Ahn Sung-Min SM, Jang Se Jin SJ, Shim Ju Hyun JH, Kim Deokhoon D, Hong Seung-Mo SM, Sung Chang Ohk CO, Baek Daehyun D, Haq Farhan F, Ansari Adnan Ahmad AA, Lee Sun Young SY, Chun Sung-Min SM, Choi Seongmin S, Choi Hyun-Jeung HJ, Kim Jongkyu J, Kim Sukjun S, Hwang Shin S, Lee Young-Joo YJ, Lee Jong-Eun JE, Jung Wang-Rim WR, Jang Hye Yoon HY, Yang Eunho E, Sung Wing-Kin WK, Lee Nikki P NP, Mao Mao M, Lee Charles C, Zucman-Rossi Jessica J, Yu Eunsil E, Lee Han Chu HC, Kong Gu GRB1, pRb, Fgf15, retinoblastoma-related 1, DmelCG7413, FBF, pp110, rbf1, Rb, Rb-1, retinoblastoma, patient, RBF, autosomal dominant, RETINOBLASTOMA 1, dRBF, hereditary retinoblastoma, Rb1, p105-Rb, RBR, eye cancer, Client., Portraits, familial retinoblastoma, Patient, Clients, RETINOBLASTOMA-RELATED PROTEIN 1, RETINOBLASTOMA-RELATED, OSRC, RB, rb, PPP1R130, ATRBR1, RETINOBLASTOMA PROTEIN, CG7413, FGF19, RbF, rbf, EG:34F3.3, trilateral, somatic mutation, Rbf1, RBF1Carcinomas, Carcinoma, WES, Complete Transcriptome, Complete, Liver, Complete Transcriptome Sequencing, Exome Sequencings, Complete Exome Sequencings, Adult Liver Cancers, Liver Cancer, Complete Exome, Hepatoma, Complete Exome Sequencing, Whole Transcriptome Sequencing, Exome, Liver Cancers, Cell Carcinoma, Liver Cell, Cancers, Adult, Hepatomas, Liver Cell Carcinoma, Sequencing, Cell Carcinomas, Exome Sequencing, Whole Exome, Liver Cell Carcinomas, Hepatocellular Carcinoma., Whole, Whole Exome Sequencing, Hepatocellular, Adult Liver Cancer, Whole Transcriptome, Transcriptome Sequencing, Adult Liver, Hepatocellular Carcinomas, Transcriptome Sequencings, CancerRB1, Dm DWnt3/5, dp53, RAS, Ras, Canonical, DWnt-5, l(1)G0098, Materials, DWnt-4, Surrogate Endpoints, p19<ARF>, dP60, Laboratory, cD1, Virus Infection, l(2)wg, BcDNA:LD15217, MYC, Myc, adult hepatoma, RBF, Ras-1, Tumor, Liver Cell Carcinoma, 11621, Chromatin Assembly, B430311C09Rik, Mutations, PI-3 kinase, p110-alpha, RBR, wnt-4, ras, c-ras2, int-1, EG:BACN5I9.1, Biological, Associations, bbl, Dm-1, Dm-2, Dm-3, DmelCG1916, CIRRH, ARF-INK4a, Whole Transcriptome, Transcriptome Sequencing, RETINOBLASTOMA PROTEIN, myc, Catnb, rbf, Fs(3)Hor, p16(INK4a), ATP-dependent chromatin remodeling, Liver cirrhosis, treatment, ISPK-1, Cell Division Cycles, Dp60, I, BCC7, dm/dMyc, beta-Tub6D, dmp53, CycD1, adult primary hepatocellular carcinoma, serum hepatitis, T, 1422/04, PI3-kinase activity, NTef2, WNT, Wnt, PI3Kgamma, Hepatocellular Carcinoma, MCAP, Dp53, Role Concepts, PI3K 68D, ccnd1a, Br, dWnt2, stage, CG17117, wnt, p50/tubulin, ATP - 1-phosphatidyl-1D-myo-inositol 3-phosphotransferase activity, Bfc, CG1799, Tumors, Fgf15, CG10873, Liver, Pathway, Viral, Ras2, RAS2, dmyc1, Ras1, RAS1, rea, Exome, familial, retinoblastoma, armadillo, CG2699, Fs(3)Sz11, Benign, Role Concept, Dm, Recrudescence, Marker, D-wnt-2, type-1 PI3K, dRas85D, Role, Cirrhosis, ATRBR1, bfy, mMyc, ras1, ras2, CG4889, HTH, Hth, BcDNA:RE36103, Carcinomas, fg, CG11621, Complete Transcriptome, S6K-alpha3, DmelCG7413, End Points, death rate, Hepatoma, Hras-1, CG3401, beta3Tub, beta3TUB, Benign Neoplasms, Dm Ras1, Immunologic, MRX19, Laboratory Marker, DmelCG4141, D-Myc, Malignant Neoplasms, APDS, DTB3, RasI, familial retinoblastoma, Material, PI3KBETA, Whole Exome Sequencing, Fu, CG2684, Fam123a, bhy, fused, dMyc1, INK4A, CG31325, Harvey-ras, CDKN2, Hras1, Wnt Signaling, CG10798, beta[[3]]-Tub, knobbly, DmelCG17117, Canonical Wnt Pathway, dm/myc, CLS, INK4, Clinical Marker, dRas, Neoplasms, developmental stage, number, CG1167, H-ras, DRAS1, 143391_i_at, DRas2, beta3 TU, IMPDH, Canonical Wnt, LFS1, PRO2286, dRBF, dMyc, dMYC, LD06825, l(3)05745, Dras2, Dras1, S6KII, PIK3, Pi3Kp60, D-Ras, PI3K-dp110, Adult Liver Cancer, Kras-2, Nop30, dPI3K, bHLHe57, anon-92Ed, anon-EST:Liang-2.13, Chromatin Disassembly, ctnnb, IMPdH, Ha-ras, Sanger sequencing, class I, Dras, ras 1, Cycles, Wnt beta Catenin Signaling Pathway, Complete, Exome Sequencings, Clinical, Liver Cancer, DmelCG6407, Recrudescences, raspberry/impd, Cell Division Cycle, Cyl-1, cell-division cycle, Dmyc, DMYc, dWnt, Pi3Kp110, Ras[V12], EK3-4, Sequencing, P110BETA, DRas, DRas85D/Ras, Neoplasias, Dmras64B, Whole Exome, Wnt3/5, DmelCG4698, PI3K21B, Nird, RNCMYC, Whole, p19ARF, D430027K22, Hepatic, prad1, beta[[3]]-tubulin, MCM, Kb, Canonical Wnt Pathways, constitutitional genetic, bHLHe39, BCL1, ccnd1, dmyc, Biologic, Ki, Cancer, Viral Infection, Cpk, RGD1562331, TP16, Dmbeta3, Complete Exome Sequencings, Malignant Neoplasm, l(2)rO727, class II, type III phosphoinositide 3-kinase activity, Serum Markers, prac, beta3t, D-ras-1, p19-lt-ARF-gt-, p16INK4a, PI(3)K, Cell, Immune Marker, cpk, E(faf), Concept, PI3K-92E/Dp110, Exome Sequencing, PIK3C1, DmelCG1167, spd, MT, CWS5, Surrogate End Point, P14ARF, p53/tubulin, chemical analysis, S35097, Neoplasm, PPP1R130, Biologic Markers, P16INK4A, CG33336, Chromatin, MRD19, RAS85D, primary cancer, Dmras85D, Hepatocellular carcinoma, l(1)9Eb, Surrogate, Chromatin Modeling, Endpoints, CG4698, D-p53, Dm-P53, Cancers, beta3, DmelCG11621, Understanding, Lds, malignant tumor, dtl, ATP-dependent chromatin remodelling, INK4a-ARF, Tub, CLOVE, betatub60D, IMD14, PI3K_68D, PI3K-92D, virulence, Dmp110, DWnt-3, DWnt-2, hereditary, DWnt-1, Neoplasia, Immune Markers, Hepatitis B, CG6407, Recovery from surgery, MTS1, Ras1/RAs85D, Biological Markers, Viral Marker, RGD1563860, determination, Dint-1, DmelCG4889, Biochemical, Endpoint, myc-B, PI3K, c-rasHa, DmelCG10798, Dp110, E(sev)3C, Pctr1, Serum, Hepatomas, betaTub3, Virus Disease, Tp53, CG11485, PPP1R49, Readability, Laboratory Markers, c-MYC, c-Myc, DMP53, DmelCG2699, Roles, kinky, RSK, Mesc, Virus, RB, rb, Virus Infections, Concepts, ARC, Arf, Dmp53, Relapses, ARF, phosphatidylinositol 3-kinase activity, Dm Wg, Wnt-4, l(2)02657, Wnt-1, D-Ras1, Wnt-3, Wnt-2, viral infection, 1323/07, c-myc, DmelCG2684, ctnnb1, Viral Diseases, RTK, rsk, Pi3K92D, CG4141, pp110, Complete Exome Sequencing, Recurrences, Whole Transcriptome Sequencing, l(1)G0436, Rb, catalyst activity, Chromatin Remodeling, Liver Fibrosis, MTS-1, Pi3k, DmP53, ras85B, ras85D, Adult, PI[[3]]K, DWnt5, DWnt4, free, DWnt3, DWnt2, genetic, B3t, DmelCG3401, Immune, D-ras-2, Markers, AA673245, Dwnt5, malignant neoplasm, Viral Markers, Dwnt4, Cell Cycles, AI316800, disease management, Therapies, P14, CG7413, P16, Pi3K, PI3k, Malignancies, P19, MCMTC, P16-INK4A, somatic mutation, Sp, Therapy, Relapse, Carcinoma, retinoblastoma-related 1, PI3K68D, l(3)s1747, Surrogate Endpoint, AU016757, P110DELTA, Ki-ras, PtdIns-3-kinase activity, rbf1, MLM, p16, Liver Cell, Biochemical Markers, infections, Biologic Marker, RETINOBLASTOMA 1, hereditary retinoblastoma, Division Cycles, beta-catenin, dPIK, 1-phosphatidylinositol 3-kinase activity, 3t, 2610028F08Rik, Hepatic Cirrhosis, clone 2.4, HCC, Signaling Pathway, NOP, Diseases, Genetic Materials, p21[Ras1], Adult Liver, dRas1, dRAS1, Fibrosis, DWint-1, Dras85D, Genetic Material, bcl-1, Tub60D, ras-2, DWnt3/5, pRb, l(1)G0354, beta-tub, l(1)G0351, 2600011E07Rik, LD02673, CRISTIN2, anon-WO03040301.228, Division Cycle, DmelCG1799, Viral Infections, c-Ha-ras, Remodeling, Wnt beta-Catenin Signaling Pathway, l(1)G0359, anon-EST:Liang-2.4, D-ras1, l(1)G0238, Viral Disease, D-ras2, WG, DmelCG33336, C-ras1, MPK-9, PI3K 68_D, Dras64B, d-myc, Treatments, C-ras2, early, l(3)06677, Myc2, l(1)G0002, p105-Rb, Niard, hth1, l(1)G0482, ftls, CG1916, p110D, hth2, myc2, Patient, Biochemical Marker, c-H-ras, Horka, l(1)G0127, Wnt Signalings, P53, Wg, Fs(3)Horka, p44, Cistron, inherited genetic, p120-PI3K, Hepatocellular Carcinomas, EG:34F3.3, MRTL, Transcriptome Sequencings, droPIK57, Rbf1, RBF1, betaTub, p50, RasV12, Clinical Markers, Complete Exome, FBF, l(1)G0139, PI3K92E, Disassembly, p53, Kras2, Chromatin Disassemblies, Benign Neoplasm, Cell Carcinoma, Gene, DmelCG9375, type I phosphatidylinositol kinase activity, Malignant, presence, autosomal dominant, rsk2, DWnt-3/5, phosphatidylinositol 3-kinase, Surrogate End Points, Cell Carcinomas, l(1)G0388, Surrogate Markers, eye cancer, anon-WO03040301.171, Client., MYCC, Liver Cell Carcinomas, p60, Cycle, OSRC, c-myc II, Fibroses, DmF2, l(1)G0380, Dp110/PI3K, PI3K-68D/E, lod, p21B, Biomarker, study, WES, dras1, Dm-ras-64B, Genetic, clone 2.13, Viruses, Infections, Malignancy, D.m.BETA-60D, Biological Marker, HU-3, Liver Cancers, Hepatitis B Virus Infection, Cell Division, PI3'K, l(1)G0391, Wnt/Wg, Wnt1, dye terminator sequencing, Wnt3, wnt4, BHLHE39, wnt3, wnt2, Ras 85D, wnt1, PI3K-68D, Immunologic Markers, Trp53, OK/SW-cl.35, Ink4a|Arf, time of survival, Clients, RSK2, Rsk2, betaTub60C, wnt5, CMM2, Signaling, beta3-tubulin, TRP53, FGF19, ras-l, Immunologic Marker, l(1)G0056, beta-Tub60D, AXIN, dP110, Disease, D11S287E, p90, Dm-HTH, P16INK4, CG9375, p120, BETA 60D, beta3-Tub, End Point, pp90RSK2, p110, K-ras, Vps34p, MAPKAPK1B, p90RSK3, Cistrons, Client, wgl, p90-RSK2, Xp53, chronic hepatitis B, PRAD1, Axin, count in organism, fs(3)05703, CTNNB, ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase activity, survival, vps34, EP(X)1093, MAPKAPK-1b, liver cirrhosis, U21B31, Infection, dp110, Ink4a/Arf, AI327039, beta[[3]] tubulin, PI3CG, AI929937, Wnt Pathway, PI-3-K, C130006E23, Serum Marker, Complete Transcriptome Sequencing, Adult Liver Cancers, PI3K-Dp110, CDK4I, Rb-1, beta60C, class III, Dwnt-2, l(3)86Ca, Dwnt-3, Wnt Signaling Pathways, p110gamma, Dm DWnt2, Su(tor)3-2, Surrogate Marker, Dm DWnt4, Rb1, Meis1, Therapeutic, Dwnt-5, P19ARF, cardinality, RETINOBLASTOMA-RELATED PROTEIN 1, RETINOBLASTOMA-RELATED, Hepatocellular, Treatment, assay, RbF, trilateral, Glafalsewhole exome sequencing of Korean hepatocellular carcinomasData Access Committee EGAC00001000329EGAC00001000329960624798001EGAS00001000604EGAD00001005361