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Somatic Mutation of Mitochondrial DNA in Cancerous and Noncancerous Liver Tissue in Individuals with Hepatocellular Carcinoma

Departments of Biochemistry [M. N., E. S., M. I.], Internal Medicine [M. N., S. N., S. S., A. T., N. K., T. T.], and Surgery [S. K., K. H., H. K.], Osaka City University Medical School, Osaka 545-8585, Japan

Unlike other types of cancer, hepatocellular carcinoma (HCC) is usually preceded by chronic inflammation caused by viral infection. The mutation of mitochondrial DNA (mtDNA) in hepatocarcinogenesis associated with viral infection was investigated. Compared with control liver tissue, the frequency of mtDNA mutations was markedly increased in both noncancerous and cancerous liver specimens from individuals with HCC. The accumulation of mtDNA mutations in HCC tissue reflected the degree of malignancy. The frequency of mtDNA mutations in HCC tissue was also greater than that described previously for other types of tumors. These observations suggest that the repeated destruction and regeneration of liver tissue associated with chronic viral hepatitis lead to the accumulation of mtDNA mutations. The genetic instability that results in the high rate of mtDNA mutation in cancerous liver tissue is also consistent with the multicentric hepatocarcinogenesis detected clinically.

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