EGAGenomicsIllumina Genome Analyzer IIx, Illumina HiSeq 2000Otherhttps://ega-archive.org/studies/EGAS00001000678EGAEGA study EGAS00001000678Whole genome sequencing of RIKEN liver cancersJapanese liver cancer RNAseqICGC-LIRI-JP Release 16Integrated analysis of whole genome and RNA sequencing in 22 HBV-associated HCCsICGC-LIRI-JP Release 15Molecular discrimination for multicentric occurrence and intrahepatic metastasis by whole genome sequencing of multiple liver cancersWGS of multi-centric liver cancers and intra-haptatic metastasis of liver cancer.Whole genome sequence of liver cancers displaying biliary phenotypeJapanese RIKEN liver cancer WGSEGArestricted<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.The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.Diverse modes of genomic alteration in hepatocellular carcinoma.International network of cancer genome projects.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 ZHudson Thomas J TJ, Anderson Warwick W, Artez Axel A, Barker Anna D AD, Bell Cindy C, Bernabé Rosa R RR, Bhan M K MK, Calvo Fabien F, Eerola Iiro I, Gerhard Daniela S DS, Guttmacher Alan A, Guyer Mark M, Hemsley Fiona M FM, Jennings Jennifer L JL, Kerr David D, Klatt Peter P, Kolar Patrik P, Kusada Jun J, Lane David P DP, Laplace Frank F, Youyong Lu L, Nettekoven Gerd G, Ozenberger Brad B, Peterson Jane J, Rao T S TS, Remacle Jacques J, Schafer Alan J AJ, Shibata Tatsuhiro T, Stratton Michael R MR, Vockley Joseph G JG, Watanabe Koichi K, Yang Huanming H, Yuen Matthew M F MM, Knoppers Bartha M BM, Bobrow Martin M, Cambon-Thomsen Anne A, Dressler Lynn G LG, Dyke Stephanie O M SO, Joly Yann Y, Kato Kazuto K, Kennedy Karen L KL, Nicolás Pilar P, Parker Michael J MJ, Rial-Sebbag Emmanuelle E, Romeo-Casabona Carlos M CM, Shaw Kenna M KM, Wallace Susan S, Wiesner Georgia L GL, Zeps Nikolajs N, Lichter Peter P, Biankin Andrew V AV, Chabannon Christian C, Chin Lynda L, Clément Bruno B, de Alava Enrique E, Degos Françoise F, Ferguson Martin L ML, Geary Peter P, Hayes D Neil DN, Hudson Thomas J TJ, Johns Amber L AL, Kasprzyk Arek A, Nakagawa Hidewaki H, Penny Robert R, Piris Miguel A MA, Sarin Rajiv R, Scarpa Aldo A, Shibata Tatsuhiro T, van de Vijver Marc M, Futreal P Andrew PA, Aburatani Hiroyuki H, Bayés Mónica M, Botwell David D L DD, Campbell Peter J PJ, Estivill Xavier X, Gerhard Daniela S DS, Grimmond Sean M SM, Gut Ivo I, Hirst Martin M, López-Otín Carlos C, Majumder Partha P, Marra Marco M, McPherson John D JD, Nakagawa Hidewaki H, Ning Zemin Z, Puente Xose S XS, Ruan Yijun Y, Shibata Tatsuhiro T, Stratton Michael R MR, Stunnenberg Hendrik G HG, Swerdlow Harold H, Velculescu Victor E VE, Wilson Richard K RK, Xue Hong H HH, Yang Liu L, Spellman Paul T PT, Bader Gary D GD, Boutros Paul C PC, Campbell Peter J PJ, Flicek Paul P, Getz Gad G, Guigó Roderic R, Guo Guangwu G, Haussler David D, Heath Simon S, Hubbard Tim J TJ, Jiang Tao T, Jones Steven M SM, Li Qibin Q, López-Bigas Nuria N, Luo Ruibang R, Muthuswamy Lakshmi L, Ouellette B F Francis BF, Pearson John V JV, Puente Xose S XS, Quesada Victor V, Raphael Benjamin J BJ, Sander Chris C, Shibata Tatsuhiro T, Speed Terence P TP, Stein Lincoln D LD, Stuart Joshua M JM, Teague Jon W JW, Totoki Yasushi Y, Tsunoda Tatsuhiko T, Valencia Alfonso A, Wheeler David A DA, Wu Honglong H, Zhao Shancen S, Zhou Guangyu G, Stein Lincoln D LD, Guigó Roderic R, Hubbard Tim J TJ, Joly Yann Y, Jones Steven M SM, Kasprzyk Arek A, Lathrop Mark M, López-Bigas Nuria N, Ouellette B F Francis BF, Spellman Paul T PT, Teague Jon W JW, Thomas Gilles G, Valencia Alfonso A, Yoshida Teruhiko T, Kennedy Karen L KL, Axton Myles M, Dyke Stephanie O M SO, Futreal P Andrew PA, Gerhard Daniela S DS, Gunter Chris C, Guyer Mark M, Hudson Thomas J TJ, McPherson John D JD, Miller Linda J LJ, Ozenberger Brad B, Shaw Kenna M KM, Kasprzyk Arek A, Stein Lincoln D LD, Zhang Junjun J, Haider Syed A SA, Wang Jianxin J, Yung Christina K CK, Cros Anthony A, Liang Yong Y, Gnaneshan Saravanamuttu S, Guberman Jonathan J, Hsu Jack J, Bobrow Martin M, Chalmers Don R C DR, Hasel Karl W KW, Joly Yann Y, Kaan Terry S H TS, Kennedy Karen L KL, Knoppers Bartha M BM, Lowrance William W WW, Masui Tohru T, Nicolás Pilar P, Rial-Sebbag Emmanuelle E, Rodriguez Laura Lyman LL, Vergely Catherine C, Yoshida Teruhiko T, Grimmond Sean M SM, Biankin Andrew V AV, Bowtell David D L DD, Cloonan Nicole N, deFazio Anna A, Eshleman James R JR, Etemadmoghadam Dariush D, Gardiner Brooke B BB, Kench James G JG, Scarpa Aldo A, Sutherland Robert L RL, Tempero Margaret A MA, Waddell Nicola J NJ, Wilson Peter J PJ, McPherson John D JD, Gallinger Steve S, Tsao Ming-Sound MS, Shaw Patricia A PA, Petersen Gloria M GM, Mukhopadhyay Debabrata D, Chin Lynda L, DePinho Ronald A RA, Thayer Sarah S, Muthuswamy Lakshmi L, Shazand Kamran K, Beck Timothy T, Sam Michelle M, Timms Lee L, Ballin Vanessa V, Lu Youyong Y, Ji Jiafu J, Zhang Xiuqing X, Chen Feng F, Hu Xueda X, Zhou Guangyu G, Yang Qi Q, Tian Geng G, Zhang Lianhai L, Xing Xiaofang X, Li Xianghong X, Zhu Zhenggang Z, Yu Yingyan Y, Yu Jun J, Yang Huanming H, Lathrop Mark M, Tost Jörg J, Brennan Paul P, Holcatova Ivana I, Zaridze David D, Brazma Alvis A, Egevard Lars L, Prokhortchouk Egor E, Banks Rosamonde Elizabeth RE, Uhlén Mathias M, Cambon-Thomsen Anne A, Viksna Juris J, Ponten Fredrik F, Skryabin Konstantin K, Stratton Michael R MR, Futreal P Andrew PA, Birney Ewan E, Borg Ake A, Børresen-Dale Anne-Lise AL, Caldas Carlos C, Foekens John A JA, Martin Sancha S, Reis-Filho Jorge S JS, Richardson Andrea L AL, Sotiriou Christos C, Stunnenberg Hendrik G HG, Thoms Giles G, van de Vijver Marc M, van't Veer Laura L, Calvo Fabien F, Birnbaum Daniel D, Blanche Hélène H, Boucher Pascal P, Boyault Sandrine S, Chabannon Christian C, Gut Ivo I, Masson-Jacquemier Jocelyne D JD, Lathrop Mark M, Pauporté Iris I, Pivot Xavier X, Vincent-Salomon Anne A, Tabone Eric E, Theillet Charles C, Thomas Gilles G, Tost Jörg J, Treilleux Isabelle I, Calvo Fabien F, Bioulac-Sage Paulette P, Clément Bruno B, Decaens Thomas T, Degos Françoise F, Franco Dominique D, Gut Ivo I, Gut Marta M, Heath Simon S, Lathrop Mark M, Samuel Didier D, Thomas Gilles G, Zucman-Rossi Jessica J, Lichter Peter P, Eils Roland R, Brors Benedikt B, Korbel Jan O JO, Korshunov Andrey A, Landgraf Pablo P, Lehrach Hans H, Pfister Stefan S, Radlwimmer Bernhard B, Reifenberger Guido G, Taylor Michael D MD, von Kalle Christof C, Majumder Partha P PP, Sarin Rajiv R, Rao T S TS, Bhan M K MK, Scarpa Aldo A, Pederzoli Paolo P, Lawlor Rita A RA, Delledonne Massimo M, Bardelli Alberto A, Biankin Andrew V AV, Grimmond Sean M SM, Gress Thomas T, Klimstra David D, Zamboni Giuseppe G, Shibata Tatsuhiro T, Nakamura Yusuke Y, Nakagawa Hidewaki H, Kusada Jun J, Tsunoda Tatsuhiko T, Miyano Satoru S, Aburatani Hiroyuki H, Kato Kazuto K, Fujimoto Akihiro A, Yoshida Teruhiko T, Campo Elias E, López-Otín Carlos C, Estivill Xavier X, Guigó Roderic R, de Sanjosé Silvia S, Piris Miguel A MA, Montserrat Emili E, González-Díaz Marcos M, Puente Xose S XS, Jares Pedro P, Valencia Alfonso A, Himmelbauer Heinz H, Quesada Victor V, Bea Silvia S, Stratton Michael R MR, Futreal P Andrew PA, Campbell Peter J PJ, Vincent-Salomon Anne A, Richardson Andrea L AL, Reis-Filho Jorge S JS, van de Vijver Marc M, Thomas Gilles G, Masson-Jacquemier Jocelyne D JD, Aparicio Samuel S, Borg Ake A, Børresen-Dale Anne-Lise AL, Caldas Carlos C, Foekens John A JA, Stunnenberg Hendrik G HG, van't Veer Laura L, Easton Douglas F DF, Spellman Paul T PT, Martin Sancha S, Barker Anna D AD, Chin Lynda L, Collins Francis S FS, Compton Carolyn C CC, Ferguson Martin L ML, Gerhard Daniela S DS, Getz Gad G, Gunter Chris C, Guttmacher Alan A, Guyer Mark M, Hayes D Neil DN, Lander Eric S ES, Ozenberger Brad B, Penny Robert R, Peterson Jane J, Sander Chris C, Shaw Kenna M KM, Speed Terence P TP, Spellman Paul T PT, Vockley Joseph G JG, Wheeler David A DA, Wilson Richard K RK, Hudson Thomas J TJ, Chin Lynda L, Knoppers Bartha M BM, Lander Eric S ES, Lichter Peter P, Stein Lincoln D LD, Stratton Michael R MR, Anderson Warwick W, Barker Anna D AD, Bell Cindy C, Bobrow Martin M, Burke Wylie W, Collins Francis S FS, Compton Carolyn C CC, DePinho Ronald A RA, Easton Douglas F DF, Futreal P Andrew PA, Gerhard Daniela S DS, Green Anthony R AR, Guyer Mark M, Hamilton Stanley R SR, Hubbard Tim J TJ, Kallioniemi Olli P OP, Kennedy Karen L KL, Ley Timothy J TJ, Liu Edison T ET, Lu Youyong Y, Majumder Partha P, Marra Marco M, Ozenberger Brad B, Peterson Jane J, Schafer Alan J AJ, Spellman Paul T PT, Stunnenberg Hendrik G HG, Wainwright Brandon J BJ, Wilson Richard K RK, Yang Huanming HWGS, NEOPL LIVER, Liver, Hepatic Cancers, primary tumour of the liver, resectable malignant neoplasm of the liver, primary tumor of the liver, Asian, Neoplasms, Cancer of Liver, primary cancer of liver, liver Cancers, adult hepatoma, hepatic, East Asian, Hepatic Neoplasm, hepatocellular carcinoma plus intrahepatic cholangiocarcinoma, Far East, primary liver cancer, School-Age, liver, School Age, Liver Neoplasm, Japanese, Neoplasm, Eastern, East, East Asian Peoples, primary, Asian People, not specified as primary or secondary, School Age Populations., School-Age Populations, Populations, Eastern Asian Peoples, ca liver - primary, Hepatic Cancer, Yamato people, Liver Cancer, primary malignant neoplasm of Liver, non-resectable primary hepatic malignant neoplasm, Cancer of the liver, adult primary hepatocellular carcinoma, Liver Cancers, Hepatic Neoplasms, Eastern Asian People, Cancers, malignant neoplasm of liver, malignant tumor of liver, Population, hepatic cancer, Far East Asian, neoplasm of liver, East Asians, malignant hepato-biliary neoplasm, Far East Asians, Resectable malignant neoplasm of Liver, primary malignant neoplasm of liver, People, Ca liver - primary, Eastern Asians, Hepatocellular Cancers, Hepatocellular, LIVER NEOPL, Hepatic, Cancer of liver, Eastern Asian, Cancer of the Liver, School-Age Population, School Age Population, hepatic neoplasm, Hepatocellular Cancer, Cancer, liver CancerHYCC1, Forms, East Asia, Neoplasms, Benign Neoplasm, post-transfusion hepatitis non A non B virus, 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protein, Gukmi1, AIP3, adult hepatoma, Profiles, 2300006C11Rik, Tumor, Liver Cell Carcinoma, P270, hTRT, Case Fatality Rates, Mutations, Death Rates, DNA Copy Number Changes, hucep-13, bbl, JTK3, Excess Mortalities, 1700124K17Rik, DNA Copy Number Variation, Catnb, Extracellular Matrices, myd, Id-1, BAF200, PICD, like-acetylglucosaminyltransferase, BCC7, Genomes, C130039L05Rik, Idpc, adult primary hepatocellular carcinoma, HLD5, Human hepatitis B virus, Mbp-1, Signatures, Hepatocellular Carcinoma, geographical area, Human Genomes, Expression Signature, IDPC, Provirus, Role Concepts, Homo sapiens disease, Age-Specific Death Rate, RING1B, ELD, Bfc, Tumors, hOSA1, uch-x4, Liver, hepatitis B virus, Viral, Crude Death, dy, armadillo, HIPI3, RING2, Benign, Role Concept, Recrudescence, Expression Signatures, mKIAA0609, Role, Copy Number Polymorphism, bfy, 5830440B04, Expression Profile, activation, mKIAA4087, Carcinomas, fg, Idh-1, death rate, TCS1, Hepatoma, Copy Number Variation, Osa1, OSA1, 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4432409D24Rik, Signature, glycosyltransferase-like protein LARGE1, PolymorphismfalseWGS of liver cancer in the Japanese populationHepatocellular carcinoma (HCC) is the third leading cancer-related cause of death and the seventh most common form of cancer worldwide, with an estimate of more than 700,000 new cases each year. The most established risk factors of HCC are chronic HBV and HCV infection. HBV infection is responsible for over 50% of the worldwide attributable risk of HCC, especially in East Asia and Africa, while in Japan and several Western countries HCV infection is the most common risk factor for HCC. To gain insights into the molecular alterations of virus-associated HCC, we performed whole genome sequencing (WGS) of 321 HCC tumors from 159 patients. This work was performed as a part of the ICGC (International Cancer Genome Consortium) project.2020-07-16 15:33:08EGAS0000100067896062515991520393554EGAD00001001881EGAD00001001643EGAD00001001996EGAD00001001035EGAD00001000842EGAD00001001642EGAD00001000809EGAD00001001880EGAD00001000808EGAC00001000010