Greta Gandolfi1, Moira Ragazzi1, Andrea Frasoldati1, Simonetta Piana1, Alessia Ciarrocchi2, Valentina Sancisi1. 1. Laboratory of Translational ResearchPathology UnitEndocrinology UnitArcispedale S. Maria Nuova-IRCCS, Viale Risorgimento 80, 42123 Reggio Emilia, Italy. 2. Laboratory of Translational ResearchPathology UnitEndocrinology UnitArcispedale S. Maria Nuova-IRCCS, Viale Risorgimento 80, 42123 Reggio Emilia, Italy Alessia.Ciarrocchi@asmn.re.it.
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. 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.
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 BRAFV600E 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 BRAFV600E and TERTC228T 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: Gustavo C Penna; Ana Pestana; José Manuel Cameselle; Denise Momesso; Fernanda Accioly de Andrade; Ana Paula Aguiar Vidal; Mario Lucio Araujo Junior; Miguel Melo; Priscila Valverde Fernandes; Rossana Corbo; Mario Vaisman; Manuel Sobrinho-Simões; Paula Soares; Fernanda Vaisman Journal: Endocrine Date: 2018-06-15 Impact factor: 3.633
Authors: Paula Soares; Antónia Afonso Póvoa; Miguel Melo; João Vinagre; Valdemar Máximo; Catarina Eloy; José Manuel Cameselle-Teijeiro; Manuel Sobrinho-Simões Journal: Endocr Pathol Date: 2021-03-02 Impact factor: 3.943