title: Germline mutation prevalence in the base excision repair gene, MYH, in patients with endometrial cancer.
abstract: 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.
authors.affiliation: Colon Cancer Genetics Group, University of Edinburgh Cancer Research Centre and MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK. rebecca.barnetson@hgu.mrc.ac.uk
authors.forename: R A
authors.initials: RA
authors.lastname: Barnetson
authors.forename: L
authors.initials: L
authors.lastname: Devlin
authors.forename: J
authors.initials: J
authors.lastname: Miller
authors.forename: S M
authors.initials: SM
authors.lastname: Farrington
authors.forename: S
authors.initials: S
authors.lastname: Slater
authors.forename: A C
authors.initials: AC
authors.lastname: Drake
authors.forename: H
authors.initials: H
authors.lastname: Campbell
authors.forename: M G
authors.initials: MG
authors.lastname: Dunlop
authors.forename: M E
authors.initials: ME
authors.lastname: Porteous
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001483:Base Sequence; D015331:Cohort Studies; D045647:DNA Glycosylases / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged
chemical_list: D017931:DNA Primers; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase