hMSH2基因在散发卵巢癌中突变研究

Analysis of Sporadic Ovarian Cancers for hMSH2 Mutations

目的：研究卵巢癌患者ＤＮＡ错配修复基因ｈＭＳＨ２（ＨｕｍａｎｍｕｔＳｈｏｍｏｌｏｇ）基因突变，同时检测其基因组微卫星Ｄ２Ｓ１２３序列变化。方法：应用ＰＣＲ、ＰＣＲ－ＳＳＣＰ和ＤＮＡ序列分析方法检测了１５例卵巢癌患者正常细胞和肿瘤细胞中的ｈＭＳＨ２基因突变。结果：３例患者存在ｈＭＳＨ２基因生殖细胞或体细胞突变，序列分析表明有碱基置换的同义突变，有碱基丢失产生的无义突变。有３例患者基因组表现Ｄ２Ｓ１２３变化，其中１例检测到ｈＭＳＨ２突变。结论：ｈＭＳＨ２基因突变和卵巢癌发生有关。机理可能为其突变引起基因组不稳定，而引起一系列基因变化。

Objective:To study the somatic and germline mutations of a human mut S homolog (hMSH2), one of a group of DNA mismatch repair gene (MMR), and microsatellite instabilities in sporadic ovarian cancers. Methods: PCR, PCR SSCP and DNA sequencing were used to find the mutations of hMSH2 and microsatellite changes. Results: Twenty percent (3/15) patients existed D2S123 instabilities. The germline and somatic mutations were found in 3 of 15 ovarian cancers. There were same sense and nonsense mutations. Conclusions: The carcinogenesis of ovarian cancers is related to the mutations of hMSH2 gene. It is postulated that the mechanism is as follows: the mutations of hMSH2 cause microsatellite instabilities and changes of a series of genes that induce cell transformation.