Molecular aspects of persistent woodchuck hepatitis virus and hepatitis B virus infection and hepatocellular carcinoma.
It seems evident that the development of fully malignant HCC is a multistage process with many variables. One possible mechanism by which many of these variables may interact is as follows. During chronic active hepatitis, viral DNA integration occurs randomly and at a low frequency in hepatocytes. Integration may be stimulated by the increased rate of hepatocyte cell division resulting from liver necrosis and regeneration during chronic disease. The presence of viral integrations in the cellular genome provides focal points for the generation of chromosomal aberrations. One pathway by which these aberrations may be generated involves rearrangement of integrated viral and cellular sequences following viral DNA integration. The rearrangements which occur may include deletion, translocation, transposition or amplification of specific viral and cellular DNA sequences. We and others have directly demonstrated that all of these events are associated with different HBV integrations. The presence of viral integrations in chromosomes may also, by some unknown mechanism, destabilize those chromosomes such that whole chromosomes fail to segregate and are lost from particular cells. Preliminary studies we have conducted using restriction fragment length polymorphisms have revealed the loss of Chromosome 11 alleles in several HCC, indicating that chromosome loss may be a common occurrence in HCC. Our studies with restriction fragment length polymorphisms support such a mechanism involving Chromosome 11 in HCC. Specific chromosomal aberrations associated with all HCCs have not yet been identified.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002869:Chromosome Aberrations; D004279:DNA, Viral; D006509:Hepatitis B / Q000235:genetics*; D006518:Hepatitis Viruses / Q000235:genetics*; D006524:Hepatitis, Viral, Animal / Q000235:genetics*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000382:microbiology*; D008392:Marmota
D004279:DNA, Viral