Activation of c-myc by woodchuck hepatitis virus insertion in hepatocellular carcinoma

Cell. 1988 Nov 18;55(4):627-35. doi: 10.1016/0092-8674(88)90221-8.


Two hepatocellular carcinomas, induced in woodchucks chronically infected with woodchuck hepatitis virus, were characterized for viral integration near c-myc and alterations of c-myc expression. In one tumor, viral integration within the untranslated region of c-myc exon 3 resulted in overexpression of a long c-myc viral cotranscript. In the second tumor, a single insertion of highly rearranged viral sequences 600 bp upstream of c-myc exon 1 was associated with increased levels of normal c-myc mRNA. In both cases, viral enhancer insertion and disruption of normal c-myc transcriptional or posttranscriptional control appear to be involved in c-myc activation. These results demonstrate that integration of woodchuck hepatitis virus near a cellular proto-oncogene, as in several retroviral models, can contribute to the genesis of liver tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • Enhancer Elements, Genetic
  • Gene Expression Regulation*
  • Hepatitis, Viral, Animal / genetics*
  • Hepatitis, Viral, Animal / microbiology
  • Liver Neoplasms, Experimental / genetics
  • Liver Neoplasms, Experimental / microbiology*
  • Marmota
  • Molecular Sequence Data
  • Oncogenes*
  • Proto-Oncogenes
  • Transcription, Genetic

Associated data

  • GENBANK/M23563
  • GENBANK/M23564