Genomic instability involved in virus-related hepatocarcinogenesis

In spite of the epidemiological link between the hepatitis C virus (HCV) infection and the incidence of hepatocellular carcinoma (HCC), there is currently no data to prove the direct oncogenicity of HCV. In this situation, we must consider not only the viral but also the nonviral factor which may accelerate hepatocarcinogenesis. Previously, we showed that a 60-bp subgenomic HBV DNA (15AB, nt 1555-1914 of HBV DNA) is a hot spot for the genomic recombination, and the cellular protein binding to 15AB may be the putative recombinogenic protein. In this paper, we show that the 15AB-like sequence exists in the human chromosomal DNA. The 15AB-binding proteins, candidates for the cellular recombinogenic protein, are now isolated and being characterized. We showed the possibility that, in HCV- as well as HBV-associated chronic active liver diseases, the recombinogenic proteins are expressed more abundantly than in the normal liver, and their functions are triggered by the binding to the recombinational hot spot in the chromosomal DNA.