Exome Sequencing of Hepatitis B Virus-Associated Hepatocellular Carcinoma

Nat Genet. 2012 Oct;44(10):1117-21. doi: 10.1038/ng.2391. Epub 2012 Aug 26.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and shows a propensity to metastasize and infiltrate adjacent and more distant tissues. HCC is associated with multiple risk factors, including hepatitis B virus (HBV) infection, which is especially prevalent in China. Here, we used exome sequencing to identify somatic mutations in ten HBV-positive individuals with HCC with portal vein tumor thromboses (PVTTs), intrahepatic metastases. Both C:G>A:T and T:A>A:T transversions were frequently found among the 331 non-silent mutations. Notably, ARID1A, which encodes a component of the SWI/SNF chromatin remodeling complex, was mutated in 14 of 110 (13%) HBV-associated HCC specimens. We used RNA interference to assess the roles of 91 of the confirmed mutated genes in cellular survival. The results suggest that seven of these genes, including VCAM1 and CDK14, may confer growth and infiltration capacity to HCC cells. This study provides a view of the landscape of somatic mutations that may be implicated in advanced HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / secondary
  • Carcinoma, Hepatocellular / virology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Chromosomes, Human, X / genetics
  • Cyclin-Dependent Kinases / genetics
  • Exome*
  • Female
  • Genetic Association Studies
  • Hepatitis B / complications*
  • Hepatitis B virus*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Portal Vein / pathology
  • Sequence Analysis, DNA
  • Transcription Factors / genetics
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Venous Thrombosis / genetics
  • Venous Thrombosis / virology

Substances

  • ARID1A protein, human
  • Nuclear Proteins
  • Transcription Factors
  • Vascular Cell Adhesion Molecule-1
  • CDK14 protein, human
  • Cyclin-Dependent Kinases