TERT promoter mutations are associated with distant metastases in papillary thyroid carcinoma.

OBJECTIVE: Transcriptional activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene were reported at high frequency in aggressive poorly differentiated and anaplastic thyroid cancers. By contrast, the relevance of these mutations in the metastatic behavior of well-differentiated thyroid cancer is still to be defined. The aim of this work was to investigate the frequency of TERT promoter mutations in a remarkable cohort of well-differentiated papillary thyroid carcinoma that developed distant metastases (DM-PTCs) and to establish whether these mutations may be predictive of metastatic behavior.

DESIGN: We analyzed the frequency of TERT promoter mutations in a group of 43 highly aggressive DM-PTCs. As controls, we analyzed these mutations in a group of 78 PTCs without distant metastases (control-PTCs). The possible correlation between TERT promoter mutations and BRAF V600E mutation was also investigated.

METHODS: TERT promoter mutational status was evaluated by direct sequencing of the hotspot harboring the C228T and the C250T mutations.

RESULTS: In the overall cohort of 121 PTCs analyzed, 17% of cases (21/121) carried a mutation in the TERT promoter. Noticeably, 33% of DM-PTCs were mutated in the TERT promoter while only 9% of the control-PTCs showed a mutation in this locus. We also observed a positive association between BRAF V600E and TERT C228T mutations in the cohort of DM-PTCs.

CONCLUSIONS: These results indicate that TERT promoter mutations are associated with the development of distant metastases in PTCs and may help in predicting aggressive behavior in this type of tumor.