EGAGenomicsIllumina HiSeq 2000;https://ega-archive.org/datasets/EGAD0000100088560EGA dataset EGAD00001000885EGA<h4>Background</h4>Hepatocellular carcinoma (HCC) is a heterogeneous disease with high mortality rate. Recent genomic studies have identified TP53, AXIN1, and CTNNB1 as the most frequently mutated genes. Lower frequency mutations have been reported in ARID1A, ARID2 and JAK1. In addition, hepatitis B virus (HBV) integrations into the human genome have been associated with HCC.<h4>Results</h4>Here, we deep-sequence 42 HCC patients with a combination of whole genome, exome and transcriptome sequencing to identify the mutational landscape of HCC using a reasonably large discovery cohort. We find frequent mutations in TP53, CTNNB1 and AXIN1, and rare but likely functional mutations in BAP1 and IDH1. Besides frequent hepatitis B virus integrations at TERT, we identify translocations at the boundaries of TERT. A novel deletion is identified in CTNNB1 in a region that is heavily mutated in multiple cancers. We also find multiple high-allelic frequency mutations in the extracellular matrix protein LAMA2. Lower expression levels of LAMA2 correlate with a proliferative signature, and predict poor survival and higher chance of cancer recurrence in HCC patients, suggesting an important role of the extracellular matrix and cell adhesion in tumor progression of a subgroup of HCC patients.<h4>Conclusions</h4>The heterogeneous disease of HCC features diverse modes of genomic alteration. In addition to common point mutations, structural variations and methylation changes, there are several virus-associated changes, including gene disruption or activation, formation of chimeric viral-human transcripts, and DNA copy number changes. Such a multitude of genomic events likely contributes to the heterogeneous nature of HCC.Diverse modes of genomic alteration in hepatocellular carcinoma.Jhunjhunwala Suchit S, Jiang Zhaoshi Z, Stawiski Eric W EW, Gnad Florian F, Liu Jinfeng J, Mayba Oleg O, Du Pan P, Diao Jingyu J, Johnson Stephanie S, Wong Kwong-Fai KF, Gao Zhibo Z, Li Yingrui Y, Wu Thomas D TD, Kapadia Sharookh B SB, Modrusan Zora Z, French Dorothy M DM, Luk John M JM, Seshagiri Somasekar S, Zhang Zemin ZVasp, VASP, Data Set., DmelCG15112, ENHANCER OF ATNSI ACTIVITY, MENA, NDPP1, l(2)02029, Enb, enb, ENA, Ena, CG15112, ENA/VASPCarcinomas, average, study, whole exome, Carcinoma, Liver, Malignant Neoplasm, Adult Liver Cancers, Hepatocellular carcinoma, Malignancy, Liver Cancer, Hepatoma, Neoplasms, Benign Neoplasm, Exomes, adult primary hepatocellular carcinoma, Liver Cancers, Benign Neoplasms, Cell Carcinoma, Liver Cell, Cancers, adult hepatoma, Tumor, Adult, Hepatomas, Malignant, Liver Cell Carcinoma, Malignant Neoplasms, Neoplasias, Cell Carcinomas, read, Benign, HCC, Liver Cell Carcinomas, Hepatocellular Carcinoma., Neoplasm, Hepatocellular, Adult Liver Cancer, Malignancies, Adult Liver, Hepatocellular Carcinomas, other neoplasm, Neoplasia, Cancer, TumorsCarcinomas, Carcinoma, Liver, Adult Liver Cancers, Hepatocellular carcinoma, Liver Cancer, Hepatoma, adult primary hepatocellular carcinoma, Liver Cancers, Cell Carcinoma, Liver Cell, Cancers, adult hepatoma, Adult, Hepatomas, Liver Cell Carcinoma, Cell Carcinomas, HCC, Liver Cell Carcinomas, Hepatocellular Carcinoma., Hepatocellular, Adult Liver Cancer, Adult Liver, Hepatocellular Carcinomas, Cancerring1b, DmelCG8445, Materials, Subgroup, RNA-seq (transcriptome sequencing), acetylglucosaminyltransferase-like protein, Gukmi1, AIP3, adult hepatoma, 2300006C11Rik, Tumor, Liver Cell Carcinoma, P270, hTRT, Transcripts, Case Fatality Rates, Mutations, Death Rates, copy_number, Discover, hucep-13, bbl, Likely, JTK3, Importance Rating Score 0, Transcriptome Sequencing, Excess Mortalities, 1700124K17Rik, Catnb, domain, Extracellular Matrices, myd, Id-1, Gene Variation Not Detected, BAF200, PICD, Progression, thymus nucleic acid, perturbation, like-acetylglucosaminyltransferase, BCC7, Genomes, C130039L05Rik, Idpc, adult primary hepatocellular carcinoma, HLD5, Human hepatitis B virus, Mbp-1, {EVENTS}, Hepatocellular Carcinoma, Mutation Abnormality, Transcript, geographical area, Poor, Malignant Germ Cell International Collaborative Risk Classification, high frequency, Human Genomes, IDPC, Provirus, Role Concepts, COPYNUM, Homo sapiens disease, Age-Specific Death Rate, RING1B, ELD, Protein Domain, Bfc, Protein Feature, Tumors, Add, hOSA1, uch-x4, Liver, hepatitis B virus, Viral, Array Feature, Low Income, Crude Death, Gene Mutation Detected, dy, armadillo, copy number, MaGIC Risk, HIPI3, Chimeric, Signed, RING2, Benign, Role Concept, chimeric, Recrudescence, mKIAA0609, Tumor Progression, Gene Variation Negative, Genetic Alteration, Role, Diverse, bfy, 5830440B04, desoxyribose nucleic acid, Disruption, activation, mKIAA4087, Carcinomas, fg, Idh-1, Alteration, IMDC Poor Risk Group, death rate, TCS1, Hepatoma, Osa1, OSA1, ding, Benign Neoplasms, INSDC_feature:gene, whole genome, surveillance, human, Genomic, DING, Malignant Neoplasms, Poor CALGB Criteria, MDC1D, Matrix Proteins, Report, Mortality Rate, bap-1, zipzap|p200, enr, AW553466, Material, Imaging Feature, WWP3, RNAseq, Whole-Transcriptome Sequencing, ds DNA, Fu, WHOLE TRANSCRIPTOME SEQUENCING, bhy, Animal Viruses, Hepatocellular., DNA, Mortality Determinant, fused, BAP004, uchl2, HYCC1, knobbly, whole exome, DNS, (Deoxyribonucleotide)n, region or site annotation, AA989761, Neoplasms, Excess, Crude Mortality Rate, LFS1, PRO2286, LARGE1, Age-Specific Death, Human, Rate, Determinant, Structural, Deoxyribonucleic Acid, Adult Liver Cancer, disease or disorder, mutation, Case Fatality, single organism cell adhesion, TP2, ctnnb, integration, alteration, Higher, Man, Gene Variant Positive, Differential Mortality, positional, Animal Virus, Excess Mortality, Liver Cancer, occurrence, Recrudescences, MDDGB6, Viral integrations, prevalence, BAF250, MAGI1c, hipi3, Double Stranded, Events, Magi-1, Deoxyribonucleic acid, Structure, Neoplasias, HUCEP-13, Gene Variation Detected, Extracellular, Crude Death Rates, genome, Not Mutated, RNA-Seq, Expression, (Deoxyribonucleotide)m, Kb, report, Methylations, Including, Ki, Cancer, SSY2, New, Probably, SMARCF1, Malignant Neoplasm, Mortality Decline, BM029, DNAn+1, Proteins, disorders, Point Mutations, Frequently, TRT, Cell, Concept, Addition, hepatitis B virus (HBV), Case Fatality Rate, Genetic Change, MT, Discovery, Human Genome, Have, 1110030E03Rik, Neoplasm, condition, background, Death, hepatitis B virus HBV, Mutation, outbreaks, integrations, MRD14, Copy Number, Death Rate, MRD19, primary cancer, Hepatocellular carcinoma, Likeliness, WTSS, Cancers, mer, malignant tumor, primary structure of sequence macromolecule, High, Protein Region, Integration, LAB_SEQ_METHOD, Differential, Extracellular Matrix, like-glycosyltransferase, Point, BAIAP1, Decline, Desoxyribonukleinsaeure, epidemics, LAMM, Virus Integrations, Neoplasia, Differential Mortalities, Extracellular Matrix Protein, Subset, Feature, Frequent, Smarcf1, Mbp1, Viral integration, Combination, Hepatomas, Highly, Tp53, PPP1R49, BAF250a, diseases, Roles, kinky, Mesc, AI314845, hEST2, DKCB4, Virus, Concepts, diseases and disorders, Relapses, merosin, viral, IMDC Poor, gene expression, multicellular organismal biosynthetic process, Total RNA Sequencing, Protein Motif, single-organism biosynthetic process, DRCTNNB1A, human disease, ctnnb1, Copy Number Reported, Gene Mutation Negative, Man (Taxonomy), Identification, Crude Mortality Rates, DKCA2, Whole Transcriptome Sequencing, Recurrences, Adult, TNRC19, Novel, Adhesions, Provirus Integration, Had, malignant neoplasm, CFR Case Fatality Rate, CDISC Events Class, Adhesion, AI316800, bap1, Event Unit, Malignancies, Double-Stranded DNA, ring2, deoxyribonucleic acids, associated, DNAn, Has, Importance Score 0, BAP1, TR, MAGI-1, Lower, Relapse, Carcinoma, Magi1d, gyltl1b-b, IDH, frequency, Modern, IDP, Reported, BAP-1, Importance 0, Liver Cell, Double-Stranded, HBV, results, IDCD, Crude Mortality, mKIAA0272, beta-catenin, (Deoxyribonucleotide)n+m, Gene Expression, Poverty, Mortality, HCC, MDDGA6, UCHL2, Diseases, Genetic Materials, B120, Adult Liver, LOWER, CG8445, KIAA0609, Region, Genetic Material, acetylglucosaminyltransferase-like 1A, Domain, Image Feature, gyltl1b, positional polypeptide feature, Mutated, Heterogeneity, mdc1d, Exomes, Mortalities, common, Features, LARGE_HUMAN, morbidity, Gene Mutant Negative, Identified, disease, Lowering, Crude Death Rate, Patient, Expressed, P53, Gene Mutation Positive, p44, AA960307, Cistron, Hepatocellular Carcinomas, Total RNA-Seq, IMDC Poor Risk, Matrix Protein, other disease, Important, human being, Mortality Declines, p53, Importance, Benign Neoplasm, Matrix, Cell Carcinoma, Gene, JAK1B, JAK1A, Matrices, mortality measurement, Malignant, froggy, Deoxyribonucleic acids, Gyltl1a, Mortality Determinants, Cell Carcinomas, Crude, hELD, Homo sapiens, Liver Cell Carcinomas, Genetic heterogeneity, Gene Variant Negative, Whole Transcriptome Shotgun Sequencing, Animal, HEL-216, AI788952, matrisome, Routine Signature, Diversity, Genetic, Viruses, Malignancy, cell adhesion molecule activity, Integrations, Liver Cancers, LARGE, Age-Specific, E030024J03Rik, hucep-6, non-neoplastic, BPFD#36, Trp53, OK/SW-cl.35, CMM9, time of survival, Clients, Mortality Rates, mortality rate, Gene Mutant Positive, Chance, p200, disorder, RNA Sequencing, Gene Mutation Not Detected, Characteristics, TRP53, AIP-3, Age Specific Death Rate, incidence, human hepatitis B virus HBV, Possess, AXIN, EVENTS, medical condition, Provirus Integrations, Cistrons, Client, Xp53, Baiap1, Axin, CTNNB, Characteristic, survival, EST2, Protein, HEL-S-26, sequence, rare (European definition), mKIAA4129, methylation, ds-DNA, Zoophaginae, Determinants, signatureText, Lowered, Rates, C1orf4, frequent, Adult Liver Cancers, Cell Adhesions, Age-Specific Death Rates, endemics, introduction, Gene Variation Positive, PFBMFT1, DEL, Modern Man, Hepatocellular, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Criteria - Poor-Risk Group, 4432409D24Rik, Inclusive, Signature, Genome, glycosyltransferase-like protein LARGE1, Motif, Chimerafalseena-DATASET-Genentech-18-07-2014-21:28:43:227-46 - samplesExome read sequences for 30 tumor-normal pairs for the study "Diverse modes of genomic alterations in Hepatocellular Carcinoma".2017-07-26 15:39:25EGAD00001000885960625159915EGAC00001000055EGAS00001000824