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

对45例散发性结直肠癌和62例胃癌进行了线粒体DNA突变分析。(1)20例结直肠癌和10例胃癌组织中检测到微卫星不稳定性(MtMSI)。在胃癌中，mtMSI多见于肠型肿瘤。(2)7例结直肠癌和6例胃癌均有相关区域改变。这些改变与mtMSI有很好的相关性。这些结果表明，mtMSI不是一种非特异性现象，而是一种特定的修复系统，如核基因组中的错配修复系统，是维持mtDNA所必需的，mtDNA改变在特定类型人类癌症的发生中可能起着特定的作用。检测与人线粒体DNA相关的错配修复基因。检测酵母中发现的人线粒体DNA的特异性错配修复基因。利用与酵母MSH1同源的聚合酶链式反应对人mtDNA进行筛选。然而，在人类线粒体DNA中没有检测到酵母MSH1或MSH2的特定基因同源。

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.