Germline mutation prevalence in the base excision repair gene, MYH, in patients with endometrial cancer.

Germline mutations in the base excision repair gene, MutY human homolog (MYH), have recently been associated with a recessively inherited multiple adenoma polyposis syndrome and colorectal cancer. The spectrum of extracolonic lesions is still being characterized, although preliminary reports suggest that bi-allelic mutation carriers may share some of the clinical features of other hereditary colon cancer syndromes. Of 225 endometrial cancer patients, we identified one individual as a compound heterozygote, carrying mutations Y165C and G382D of MYH, and five individuals with heterozygous defects (three G382D and two Y165C). The patient with the bi-allelic Y165C/G382D mutation also had a sebaceous carcinoma, a feature of Muir-Torre syndrome. Although several intronic polymorphisms were detected in the heterozygous carriers, no other pathogenic variants were identified. While not conclusive, this novel and interesting finding provides evidence that bi-allelic germline mutations in MYH may increase susceptibility to endometrial cancer.