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

人类肿瘤中线粒体DNA的改变及其分子机制分析

• 批准号: 12670173
• 负责人: NAKAMURA Shin-ichi
• 金额: $ 2.3万
• 依托单位: Iwate Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670173/
• 关键词: mitochondria DNA; gastric cancer; colorectal cancer; microsatellite instability; mismatch repair gene; MSH1; MSH2; microsatellite instabiliy

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.

1.人类肿瘤中线粒体DNA的突变对45例散发性结直肠癌和62例胃癌的线粒体DNA(mtDNA)突变进行了分析。 (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 束中的微卫星不稳定性 (mtMSI)。在胃癌中，mtMSI 经常在肠型肿瘤中检测到。 (2)结直肠癌7例、胃癌6例出现索状区改变。这些改变与 mtMSI 密切相关。这些结果表明，mtMSI并不是一种非特异性现象，而是mtDNA的维持需要一定的修复系统，如核基因组中的错配修复系统，并且mtDNA的改变可能在特定类型人类癌症的肿瘤发生中发挥特定作用。2．人类线粒体DNA错配修复基因的检测。检测酵母中发现的特定人类线粒体DNA错配修复基因。使用与酵母MSH1同源的PCR引物来筛选人线粒体DNA。然而，在人类线粒体 DNA 中并未检测到酵母 MSH1 或 MSH2 的特定基因同源物。

项目成果

Habano W, Nakamura S, Sugai T: "Microsatellite instability in the mitochondrial DNA of colorectal carcinomas : Evidence for mismatch repair systems in mitochondrial genome"Oncogene. 17. 1931-1937 (1998)

Habano W、Nakamura S、Sugai T：“结直肠癌线粒体 DNA 中的微卫星不稳定性：线粒体基因组中错配修复系统的证据”Oncogene。

Habano W, Sugai T, Yoshida T, Nakamura S: "Mitochondrial gene mutation, but not large-scale deletion, is a feature of colorectal carcinomas with mitochondrial microsatellite instability"Int J Cancer. 83. 625-629 (1999)

Habano W、Sugai T、Yoshida T、Nakamura S：“线粒体基因突变，但不是大规模缺失，是具有线粒体微卫星不稳定的结直肠癌的一个特征”Int J Cancer。

Habano W, Sugai T, Nakamura S, Uesugi N, Yoshida T, Sasou S: "Microsatellite instability and mutation of mitochondrial and nuclear DNA in gastric carcinoma"Gastroenterology. 118. 835-841 (2000)

Habano W、Sugai T、Nakamura S、Uesugi N、Yoshida T、Sasou S：“胃癌中线粒体和核 DNA 的微卫星不稳定性和突变”胃肠病学。

Habano W, Nakamura S: "Reply to : S0matic mutations in mitochondrial DNA do not associate with nuclear microsatellite instability in gastric cancer"Gastroenterology. 119. 1806-1808 (2000)

Habano W、Nakamura S：“回复：线粒体 DNA 中的 S0matic 突变与胃癌中的核微卫星不稳定性无关”胃肠病学。

Habano W,Nakamura S,Sugai T: "Microsatellite instability in the mitochondrial DNA of colorectal carcinomas Evidence for mismatch repair systems in mitochondrial genome"Oncogene. 17. 1931-1937 (1998)

Habano W、Nakamura S、Sugai T：“结直肠癌线粒体 DNA 中的微卫星不稳定性线粒体基因组中错配修复系统的证据”癌基因。