Woodchuck hepatitis virus DNA integration in a common chromosomal region of the woodchuck genome in two independent hepatocellular carcinomas

Arch Virol. 1997;142(3):499-509. doi: 10.1007/s007050050096.

Abstract

In woodchuck hepatocellular carcinoma (HCC) the myc-oncogene family (particularly N-myc2) and the win locus of cellular genome have been reported as frequent targets for integration of woodchuck hepatitis virus (WHV) DNA. In this paper a further cellular locus, b3n, is reported as recurrent target for WHV integration in woodchuck HCC. Cloning and sequencing of a WHV-DNA integration and its cellular flanking regions showed that viral DNA was inserted in a chromosomal region already described for WHV integration in another single HCC. The two integration sites are only 0.5 kb apart. A link between WHV integration in b3n and HCC development may be postulated. Careful analysis of the sequence of the unoccupied locus revealed that, in addition to Alu-like repeats and a gag-like coding region, already described, several features of Matrix Attachment Region (MAR) sequences are present. Thus (part of) b3n might be a previously unrecognized MAR. Organization of the chromatin in functional domains and regulation of gene expression are some functions attributed to MAR sequences. The occurrence of WHV-DNA integration close to the same putative MAR in two different HCCs suggests that a mechanism of deregulation of MAR functions by WHV insertion might act in some liver tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / virology*
  • Chromosome Mapping
  • DNA, Neoplasm*
  • DNA, Viral*
  • Female
  • Hepatitis B Virus, Woodchuck / genetics*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / virology*
  • Marmota
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Polymerase Chain Reaction
  • Virus Integration*

Substances

  • DNA, Neoplasm
  • DNA, Viral

Associated data

  • GENBANK/X90998