title: Evaluation of germline PTEN mutations in endometrial cancer patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Gynecology and Breast Research Laboratory, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
authors.forename: Destin
authors.initials: D
authors.lastname: Black
authors.forename: Faina
authors.initials: F
authors.lastname: Bogomolniy
authors.forename: Mark E
authors.initials: ME
authors.lastname: Robson
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.forename: Richard R
authors.initials: RR
authors.lastname: Barakat
authors.forename: Jeff
authors.initials: J
authors.lastname: Boyd
mesh_terms: D015331:Cohort Studies; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human