Kobayashi K, Matsushima M, Koi S, Saito H, Sagae S, Kudo R, Nakamura Y
Laboratory of Molecular Medicine, Institute of Medical science, University of Tokyo, Japan.
Jpn J Cancer Res. 1996 Feb;87(2):141-5. doi: 10.1111/j.1349-7006.1996.tb03151.x.
Microsatellite instability, monitored by replication error (RER), has been observed in both sporadic and hereditary types of endometrial carcinoma. In the hereditary tumors, this instability is considered to be caused by a germline defect in the DNA mismatch-repair system. We previously reported that nearly one-quarter of sporadic endometrial carcinomas examined revealed an RER-positive phenotype at multiple microsatellite loci. To investigate the role of genetic alterations of DNA mismatch-repair genes in sporadic endometrial carcinomas, we screened 18 RER(+) endometrial carcinomas for mutations of hMLH1 and hMSH2. Although we found no germline mutations, we detected two somatic mutations of hMLH1 in a single endometrial cancer; these two mutations had occurred on different alleles, suggesting that two separate mutational events had affected both copies of hMLH1 in this particular tumor. These data implied that mutations of hMLH1 or hMSH2 play limited roles in the development of sporadic endometrial carcinomas, and that the tumors with genetic instability might have alterations of other mismatch-repair genes, such as hPMS1 and hPMS2, or of unknown genes related to the mismatch-repair system.
通过复制错误（RER）监测的微卫星不稳定性在散发性和遗传性子宫内膜癌中均有观察到。在遗传性肿瘤中，这种不稳定性被认为是由DNA错配修复系统中的种系缺陷引起的。我们之前报道，在检测的散发性子宫内膜癌中，近四分之一在多个微卫星位点显示出RER阳性表型。为了研究DNA错配修复基因的遗传改变在散发性子宫内膜癌中的作用，我们对18例RER（+）子宫内膜癌进行了hMLH1和hMSH2突变筛查。虽然我们未发现种系突变，但在一例子宫内膜癌中检测到hMLH1的两个体细胞突变；这两个突变发生在不同等位基因上，表明在这个特定肿瘤中，两个独立的突变事件影响了hMLH1的两个拷贝。这些数据表明，hMLH1或hMSH2的突变在散发性子宫内膜癌的发生中作用有限，并且具有遗传不稳定性的肿瘤可能存在其他错配修复基因（如hPMS1和hPMS2）或与错配修复系统相关的未知基因的改变。
