The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients

Genome Res. 2012 Apr;22(4):593-601. doi: 10.1101/gr.133926.111. Epub 2012 Jan 20.


Hepatitis B virus (HBV) infection is a leading risk factor for hepatocellular carcinoma (HCC). HBV integration into the host genome has been reported, but its scale, impact and contribution to HCC development is not clear. Here, we sequenced the tumor and nontumor genomes (>80× coverage) and transcriptomes of four HCC patients and identified 255 HBV integration sites. Increased sequencing to 240× coverage revealed a proportionally higher number of integration sites. Clonal expansion of HBV-integrated hepatocytes was found specifically in tumor samples. We observe a diverse collection of genomic perturbations near viral integration sites, including direct gene disruption, viral promoter-driven human transcription, viral-human transcript fusion, and DNA copy number alteration. Thus, we report the most comprehensive characterization of HBV integration in hepatocellular carcinoma patients. Such widespread random viral integration will likely increase carcinogenic opportunities in HBV-infected individuals.

MeSH terms

  • Base Sequence
  • Binding Sites / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Genome, Human / genetics*
  • Hepatitis B / genetics*
  • Hepatitis B / virology
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / physiology
  • Host-Pathogen Interactions / genetics
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology
  • Male
  • Molecular Sequence Data
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Sequence Analysis, DNA / methods
  • Transcriptome / genetics
  • Virus Integration / genetics*

Associated data

  • GEO/GSE34957