title: Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model.
abstract: The most common risk factor for developing hepatocellular carcinoma (HCC) is chronic infection with hepatitis B virus (HBV). To better understand the evolutionary forces driving HCC, we performed a near-saturating transposon mutagenesis screen in a mouse HBV model of HCC. This screen identified 21 candidate early stage drivers and a very large number (2,860) of candidate later stage drivers that were enriched for genes that are mutated, deregulated or functioning in signaling pathways important for human HCC, with a striking 1,199 genes being linked to cellular metabolic processes. Our study provides a comprehensive overview of the genetic landscape of HCC.
authors: Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore.
authors: Emilie A
authors: EA
authors: Bard-Chapeau
authors: Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore.
authors: Anh-Tuan
authors: AT
authors: Nguyen
authors: Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH, UK.
authors: Alistair G
authors: AG
authors: Rust
authors: Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore.
authors: Ahmed
authors: A
authors: Sayadi
authors: Clinical Imaging Research Centre, National University of Singapore, Centre for Translation Medicine, 14 Medical Drive, #B1-01, 117599, Singapore.
authors: Philip
authors: P
authors: Lee
authors: Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore.
authors: Belinda Q
authors: BQ
authors: Chua
authors: Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, 117543, Singapore.
authors: Lee-Sun
authors: LS
authors: New
authors: Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam.
authors: Johann
authors: J
authors: de Jong
authors: Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore.
authors: Jerrold M
authors: JM
authors: Ward
authors: Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore.
authors: Christopher Ky
authors: CK
authors: Chin
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore.
authors: Valerie
authors: V
authors: Chew
authors: National Cancer Centre, Singapore.
authors: Han Chong
authors: HC
authors: Toh
authors: Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore.
authors: Jean-Pierre
authors: JP
authors: Abastado
authors: Cancer Science Institute of Singapore, National University of Singapore, Department of Pathology, National University Health System, Singapore.
authors: Touati
authors: T
authors: Benoukraf
authors: Cancer Science Institute of Singapore, National University of Singapore, Department of Pathology, National University Health System, Singapore.
authors: Richie
authors: R
authors: Soong
authors: Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore.
authors: Frederic A
authors: FA
authors: Bard
authors: Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242.
authors: Adam J
authors: AJ
authors: Dupuy
authors: Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Randy L
authors: RL
authors: Johnson
authors: Clinical Imaging Research Centre, National University of Singapore, Centre for Translation Medicine, 14 Medical Drive, #B1-01, 117599, Singapore.
authors: George K
authors: GK
authors: Radda
authors: Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, 117543, Singapore.
authors: Eric Cy
authors: EC
authors: Chan
authors: Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam.
authors: Lodewyk Fa
authors: LF
authors: Wessels
authors: Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH, UK.
authors: David J
authors: DJ
authors: Adams
authors: Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore.
authors: Nancy A
authors: NA
authors: Jenkins
authors: Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore.
authors: Neal G
authors: NG
authors: Copeland
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D004251:DNA Transposable Elements; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D016254:Mutagenesis, Insertional; D019289:Pyruvic Acid / Q000378:metabolism
chemical_list: D004251:DNA Transposable Elements; D019289:Pyruvic Acid