Molecular aspects of hepatocarcinogenesis and their clinical implications - review

The formation and development of cancer is associated with various genetic abnormalities. Recent progress in the study of genetic changes in hepatocellular carcinoma (HCC) have clarified the aberrations of oncogenes and tumor suppressor genes, as well as the role of the hepatitis virus in hepatocarcinogenesis. Overexpression of the c-myc gene, inactivation of the p53 and RB genes, and the loss of heterozygosity (LOH) of some chromosomes where tumor suppressor genes may be located have been reported in association with the progression of HCC. However, genetic abnormalities of HCC at the early stages have yet to be elucidated. On the other hand, the association between HCC and chronic infection with the hepatitis virus also shows the relevance of the oncogenic potential of the hepatitis virus to HCC formation. Some regions of HBV genome, especially the HBV X gene, stimulate the various cellular activities related to tumor promotion and contribute to hepatocarcinogenesis. The knowledge of genetic abnormalities is helpful in the elucidation of pathogenesis and probably in the diagnosis, prognosis and therapy of HCC. Further studies of these genetic changes will apparently promote molecular diagnosis and gene therapy in HCC.