Frequency of Germline PTEN Mutations in Differentiated Thyroid Cancer

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%. Conclusion: 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.