Abstract
Lynch syndrome is a hereditary cancer predisposition syndrome inherited in an autosomal dominant manner and associated with deficiency of the mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2. We report a 52-year-old female case of synchronous triple cancers associated with a large deletion in MSH2 gene without a distinct family history of Lynch syndrome. The patient underwent simultaneous operation for cecum cancer, descending colon cancer and endometrial cancer at the age of 52. Due to the presence of MSI-H in resected tumor tissues of all 3 lesions, Lynch syndrome was suspected. Since germline mutation analysis of mismatch repair genes MLH1, MSH2 and MSH6 by direct sequencing showed no deleterious mutation, MLPA analysis of MLH1 and MSH2 was performed and detected a large deletion encompassing exons 14-16 of MSH2. In the context of breakpoint analysis, long-PCR combined with direct sequencing for 3’ downstream of MSH2 was carried out and consequently large deletion 36.7 kb in extent was identified. The mutation found in this study is novel one that has not been reported previously. It seems to be possible to accomplish rational surveillance based on prospect for prognosis and predictive testing for at risk persons by detailed examination of mutations in MMR genes, and that could substantiate a practical management for patients and families.
