HEPATITIS-B VIRUS AND HEPATOCELLULAR-CARCINOMA

Hepatocellular carcinomas in woodchuck were characterized for woodchuck hepatitis virus integration near c-myc oncogene. In one tumor, viral integration resulted in overexpression of a c-myce exon 1, was associated with increased levels of normal c-myc mRNA. These results demonstrate that integration of woodchuck hepatitis virus near a proto-oncogene can contribute to the genesis of liver tumors. From a comparison of a single hepatitis B virus (HBV) integration site in a human hepatoma with the corresponding unoccupied site have shown HBV DNA insertion in a putative cellular exon. This exon presented striking similarity to the DNA-binding domain of the thyroid/steroid hormones receptors. The corresponding cDNA has been isolated (hap gene) a shown to encode the retinoic acid receptor. It is most probable that consequent to HBV insertion, has became inappropriately expressed as an altered chimaeric gene retinoic acid receptor, thus contributing to the cell transformation. As for woodchuck these results strongly support the possibility that HBV may play a direct role in liver carcinogenesis by insertional mutagenesis.