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

Nat Genet. 2014 Jan;46(1):24-32. doi: 10.1038/ng.2847. Epub 2013 Dec 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / virology*
  • DNA Transposable Elements
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic
  • Hepatitis B, Chronic / complications*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / virology*
  • Metabolic Networks and Pathways / genetics
  • Metabolomics / methods
  • Mice
  • Mice, Transgenic
  • Mutagenesis*
  • Mutagenesis, Insertional
  • Pyruvic Acid / metabolism

Substances

  • DNA Transposable Elements
  • Pyruvic Acid