Evaluation of germline PTEN mutations in endometrial cancer patients

Cowden Syndrome is a rare autosomal dominant disorder characterized by multiple hamartomas, increased risks of breast and thyroid cancers, and possibly endometrial carcinoma. Susceptibility to Cowden syndrome is conferred by germline mutation of the PTEN tumor suppressor gene, and somatic mutations of PTEN are common in sporadic endometrial carcinomas. The aim of this study was to test whether a substantial proportion of endometrial cancers are associated with germline mutations of the PTEN gene, not necessarily in association with clinically overt Cowden syndrome.

A retrospective cohort of 240 consecutive patients with pathologically confirmed endometrial carcinoma diagnosed at our institution from 1999 to 2002 was ascertained for study. Genomic DNA was isolated from peripheral blood lymphocytes and the entire PTEN coding region and exon-intron junctions were screened for mutations by single strand conformation polymorphism analysis. Potential variants were subjected to direct sequence analysis.

No clearly deleterious PTEN sequence variant was identified in this screened cohort of endometrial cancer patients. One patient harbored a 5-bp deletion in the intronic region adjacent to the splice acceptor site of PTEN exon 4, but this variant has been previously classified as a rare polymorphism.

Although these data do not preclude the possibility of an increased risk of endometrial cancer in association with the Cowden syndrome, they indicate that germline PTEN mutations do not account for a significant proportion of genetic attributable risk for endometrial carcinoma.