Alteration of mitochondrial DNA in human tumors and analysis of its molecular mechanism

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1. Mutation of a mitochondrial DNA in human tumorsA mutation of the mitochondrial DNA (mtDNA) was analyzed in 45 cases of sporadic colorectal carcinoma and in 62 cases of gastric carcinoma. (1) Microsatellite instability (mtMSI) in a polycytidine (C)n tract within a non-coding region was detected in 20 colorectal carcinomas and 10 gastric carcinomas. In gastric carcinoma, mtMSI was frequently detected in intestinal type tumors. (2) Alteration in cording regions were found in 7 cases of colorectal carcinoma and in 6 cases of gastric carcinoma. These alterations correlated well with mtMSI. These results suggested that mtMSI is not a nonspecific phenomenon but a certain repair systems, like the mismatch repair systems in the nuclear genome, are required for mtDNA maintenance and that mtDNA alteration may play a specific role in the tumorigenesis of specific type human carcinoma.2. Detection of mismatch repair gene concerning the human mtDNA.To detect a specific mismatch repair gene for human mtDNA, which has been found in yeast. PCR primers homologous of yeast MSH1 were used for the screening of human mtDNA. Specific gene homologue of yeast MSH1 or MSH2, however, did not detected in the human mtDNA.