Germline Mutation Analysis of DNA Mismatch Repair (MMR) Gene in Endometrial Cancer Patients with Familial Predisposition to Cancer

Abstract

Some cases of endometrial carcinoma are thought to be associated with a familial tumor, hereditary non-polyposis colorectal cancer （HNPCC）, and their development may be due to mutation of the MMR gene in germ cell. In this study, we examined 36 cases of endometrial carcinoma associated with familial predisposition to cancer or double cancer, and analyzed germ cell mutations in 3 MMR genes （hMLH1, hMSH2 and hMSH6） to elucidate the pathogenesis. MMR gene mutations in germ cells were detected in 6 of 36 patients （16.6%）. The most frequent mutation was a frame shift in the hMSH6 gene, which was identified in 3 patients. None of the 6 patients with mutations met the current clinical diagnostic criteria for HNPCC. MMR gene mutations in germ cells were detected at high frequency by taking into account familial predisposition to cancer in patients with endometrial carcinoma. Furthermore, mutations in the hMSH6 gene may be particularly important for carcinogenesis of this tumor.