Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 44 (7), 765-9

Genome-wide Survey of Recurrent HBV Integration in Hepatocellular Carcinoma

Affiliations

Genome-wide Survey of Recurrent HBV Integration in Hepatocellular Carcinoma

Wing-Kin Sung et al. Nat Genet.

Abstract

To survey hepatitis B virus (HBV) integration in liver cancer genomes, we conducted massively parallel sequencing of 81 HBV-positive and 7 HBV-negative hepatocellular carcinomas (HCCs) and adjacent normal tissues. We found that HBV integration is observed more frequently in the tumors (86.4%) than in adjacent liver tissues (30.7%). Copy-number variations (CNVs) were significantly increased at HBV breakpoint locations where chromosomal instability was likely induced. Approximately 40% of HBV breakpoints within the HBV genome were located within a 1,800-bp region where the viral enhancer, X gene and core gene are located. We also identified recurrent HBV integration events (in ≥ 4 HCCs) that were validated by RNA sequencing (RNA-seq) and Sanger sequencing at the known and putative cancer-related TERT, MLL4 and CCNE1 genes, which showed upregulated gene expression in tumor versus normal tissue. We also report evidence that suggests that the number of HBV integrations is associated with patient survival.

Similar articles

See all similar articles

Cited by 258 PubMed Central articles

See all "Cited by" articles

References

    1. Oncogene. 2001 Sep 27;20(43):6233-40 - PubMed
    1. BMC Cancer. 2009 Nov 03;9:389 - PubMed
    1. Nature. 1980 Jul 31;286(5772):533-5 - PubMed
    1. Pharmacogenomics. 2007 Aug;8(8):997-1003 - PubMed
    1. Nat Genet. 2011 May;43(5):464-9 - PubMed

Publication types

MeSH terms

Associated data

LinkOut - more resources

Feedback