title: Frequency of germline PTEN mutations in differentiated thyroid cancer.
abstract: BACKGROUND
  Differentiated thyroid cancer (DTC) is seen in 3%-10% of individuals carrying a germline PTEN mutation. Patients with PTEN mutations are at risk for additional neoplasms as are their affected offspring. However, the frequency of PTEN mutations among DTC cases has not been systematically analyzed. The objective of this study was to determine the frequency of PTEN mutations in an unselected group of patients with DTC and to identify whether additional clinical features might indicate the need for referral for genetic counseling and possible testing.
  
  
  METHODS
  We collected personal medical and family history information, head circumference data, and blood from 259 consecutively identified clinic-based patients with DTC, unselected for personal or family history. Individuals were categorized for diagnostic criteria for Cowden syndrome (CS) using the 2009 National Comprehensive Cancer Network (NCCN) guidelines and underwent germline PTEN mutation analysis.
  
  
  RESULTS
  Two of the 259 patients (0.8%), with both follicular thyroid carcinoma and macrocephaly, were found to carry a germline mutation in the PTEN gene. The PTEN mutation frequency in unselected cases of follicular thyroid carcinoma was 4.8%.
  
  
  CONCLUSIONS
  The frequency of germline pathogenic PTEN mutations in an unselected series of patients with DTC is relatively low, but it is enriched by considering follicular histology and macrocephaly. These results suggest that by adding head circumference to the clinical assessment, thyroid cancer specialists can more effectively identify patients needing referral for cancer genetic services.
authors.affiliation: Division of Human Genetics, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, Ohio 43240, USA. rebecca.nagy@osumc.edu
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nagy
authors.forename: Shireen
authors.initials: S
authors.lastname: Ganapathi
authors.forename: Ilene
authors.initials: I
authors.lastname: Comeras
authors.forename: Charissa
authors.initials: C
authors.lastname: Peterson
authors.forename: Mohammed
authors.initials: M
authors.lastname: Orloff
authors.forename: Kyle
authors.initials: K
authors.lastname: Porter
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Ringel
authors.forename: Richard T
authors.initials: RT
authors.lastname: Kloos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D002648:Child; D018095:Germ-Line Mutation; D006801:Humans; D058627:Megalencephaly / Q000235:genetics; D008875:Middle Aged; D008957:Models, Genetic; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human