Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model

Emilie A Bard-Chapeau; Anh-Tuan Nguyen; Alistair G Rust; Ahmed Sayadi; Philip Lee; Belinda Q Chua; Lee-Sun New; Johann de Jong; Jerrold M Ward; Christopher Ky Chin; Valerie Chew; Han Chong Toh; Jean-Pierre Abastado; Touati Benoukraf; Richie Soong; Frederic A Bard; Adam J Dupuy; Randy L Johnson; George K Radda; Eric Cy Chan; Lodewyk Fa Wessels; David J Adams; Nancy A Jenkins; Neal G Copeland

doi:10.1038/ng.2847

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Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model

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Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model

Emilie A Bard-Chapeau, Anh-Tuan Nguyen, Alistair G Rust, Ahmed Sayadi, Philip Lee, Belinda Q Chua, Lee-Sun New, Johann de Jong, Jerrold M Ward, Christopher Ky Chin, …

Nature genetics, Vol.46(1), pp.24-32

01/2014

DOI: 10.1038/ng.2847

PMCID: PMC4131144

PMID: 24316982

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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.

Mutagenesis

Liver Neoplasms - virology

Liver Neoplasms - genetics

Humans

Gene Expression Regulation, Neoplastic

Mice, Transgenic

Carcinoma, Hepatocellular - virology

Metabolomics - methods

DNA Transposable Elements

Metabolic Networks and Pathways - genetics

Animals

Hepatitis B, Chronic - complications

Carcinoma, Hepatocellular - genetics

Liver Neoplasms - metabolism

Pyruvic Acid - metabolism

Mice

Mutagenesis, Insertional

Carcinoma, Hepatocellular - metabolism

Disease Models, Animal

Details

Title: Subtitle: Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model
Creators: Emilie A Bard-Chapeau - Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore
Anh-Tuan Nguyen - Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore
Alistair G Rust - Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH, UK
Ahmed Sayadi - Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore
Philip Lee - Clinical Imaging Research Centre, National University of Singapore, Centre for Translation Medicine, 14 Medical Drive, #B1-01, 117599, Singapore
Belinda Q Chua - Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore
Lee-Sun New - Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, 117543, Singapore
Johann de Jong - Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam
Jerrold M Ward - Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore
Christopher Ky Chin - Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore
Valerie Chew - Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore
Han Chong Toh - National Cancer Centre, Singapore
Jean-Pierre Abastado - Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore
Touati Benoukraf - Cancer Science Institute of Singapore, National University of Singapore, Department of Pathology, National University Health System, Singapore
Richie Soong - Cancer Science Institute of Singapore, National University of Singapore, Department of Pathology, National University Health System, Singapore
Frederic A Bard - Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore
Adam J Dupuy - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242
Randy L Johnson - Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA
George K Radda - Clinical Imaging Research Centre, National University of Singapore, Centre for Translation Medicine, 14 Medical Drive, #B1-01, 117599, Singapore
Eric Cy Chan - Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, 117543, Singapore
Lodewyk Fa Wessels - Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam
David J Adams - Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH, UK
Nancy A Jenkins - Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore
Neal G Copeland - Institute Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore
Resource Type: Journal article
Publication Details: Nature genetics, Vol.46(1), pp.24-32
DOI: 10.1038/ng.2847
PMID: 24316982
PMCID: PMC4131144
NLM abbreviation: Nat Genet
ISSN: 1061-4036
eISSN: 1546-1718
Publisher: United States
Grant note: 13031 / Cancer Research UK Cancer Research UK Wellcome Trust P30 CA016672 / NCI NIH HHS A13031 / Cancer Research UK
Language: English
Date published: 01/2014
Academic Unit: Anatomy and Cell Biology; Pathology
Record Identifier: 9984025442902771

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