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

1.本文对45例散发性大肠癌和62例胃癌的线粒体DNA进行了突变分析。(1)在20例结直肠癌和10例胃癌中检测到非编码区多胞苷（C）n序列的微卫星不稳定性（mtMSI）。在胃癌中，mtMSI多见于肠型肿瘤。(2)结直肠癌7例，胃癌6例。这些改变与mtMSI密切相关。这些结果表明，线粒体不稳定性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，对线粒体DNA的维持是必需的，线粒体DNA的改变可能在特定类型的人类肿瘤的发生中起着特定的作用.人类线粒体DNA错配修复基因的检测：检测在酵母中发现的人类线粒体DNA特异性错配修复基因。用与酵母MSH1同源的PCR引物筛选人mtDNA。在人mtDNA中未检测到与酵母菌MSH1或MSH2同源的基因。

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.