Journal
CLINICAL ENDOCRINOLOGY
Volume 85, Issue 2, Pages 283-290Publisher
WILEY
DOI: 10.1111/cen.12999
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Funding
- NHMRC [1061941]
- Fondation de France
- Inserm - University of Sydney Research Mobility Funding Scheme
- National Health and Medical Research Council of Australia [1061941] Funding Source: NHMRC
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ContextTERT promoter mutations have been associated with adverse prognosis in papillary thyroid carcinomas (PTCs). ObjectiveWe investigated the association between TERT promoter mutations and survival from PTC. DesignRetrospective observational cohort study. PatientsEighty consecutive patients with PTC who underwent surgery between 1990 and 2003. MeasurementsTERT promoter was genotyped in DNA from 80 archival PTCs by Sanger sequencing. Median follow-up was 106months (range 1-270). Outcomes analysis was stratified according to disease and overall survival status. For each parameter, relative risk (RR) adjusted for age at first surgery and gender was estimated. Both univariate and multivariate analyses were performed using logistic regression, Kaplan-Meier survival analysis and Cox regression models. ResultsPTCs from 11 patients (14%) contained either C228T or C250T TERT promoter mutation. TERT mutations were significantly associated with adverse prognostic features such as older age (P=0002), male gender (P=001) and Stage IV disease (P=003). Four patients died from PTC during follow-up: 3 patients with TERT mutations (27%) and one without (15%). Disease-related mortality rate with or without TERT mutations was 337 vs 16 per 1000 patient-years respectively, that is 10 (95% CI=10-1041, P=005) fold higher, after adjustment for age at first surgery and gender. The combination of TERT promoter mutation and BRAF(V600E) significantly increased disease-related death risk (P=0002). TERT mutations increased expression of a reporter gene in thyroid cells containing BRAF(V600E). ConclusionsTERT promoter mutations are a major indicator of death due to PTCs. Conversely, absence of TERT mutations portends better survival.
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