title: TERT promoter mutations are associated with distant metastases in papillary thyroid carcinoma.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Laboratory of Translational ResearchPathology UnitEndocrinology UnitArcispedale S. Maria Nuova-IRCCS, Viale Risorgimento 80, 42123 Reggio Emilia, Italy.
authors.forename: Greta
authors.initials: G
authors.lastname: Gandolfi
authors.affiliation: Laboratory of Translational ResearchPathology UnitEndocrinology UnitArcispedale S. Maria Nuova-IRCCS, Viale Risorgimento 80, 42123 Reggio Emilia, Italy.
authors.forename: Moira
authors.initials: M
authors.lastname: Ragazzi
authors.affiliation: Laboratory of Translational ResearchPathology UnitEndocrinology UnitArcispedale S. Maria Nuova-IRCCS, Viale Risorgimento 80, 42123 Reggio Emilia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Frasoldati
authors.affiliation: Laboratory of Translational ResearchPathology UnitEndocrinology UnitArcispedale S. Maria Nuova-IRCCS, Viale Risorgimento 80, 42123 Reggio Emilia, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Piana
authors.affiliation: Laboratory of Translational ResearchPathology UnitEndocrinology UnitArcispedale S. Maria Nuova-IRCCS, Viale Risorgimento 80, 42123 Reggio Emilia, Italy Alessia.Ciarrocchi@asmn.re.it.
authors.forename: Alessia
authors.initials: A
authors.lastname: Ciarrocchi
authors.affiliation: Laboratory of Translational ResearchPathology UnitEndocrinology UnitArcispedale S. Maria Nuova-IRCCS, Viale Risorgimento 80, 42123 Reggio Emilia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sancisi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D002291:Carcinoma, Papillary; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: C509186:TERT protein, human; D019098:Telomerase