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TERT promoter mutations are a major indicator of recurrence and death due to papillary thyroid carcinomas

CONTEXT: TERT promoter mutations have been associated with adverse prognosis in papillary thyroid carcinomas (PTCs). OBJECTIVE: We investigated the association between TERT promoter mutations and survival from PTC. DESIGN: Retrospective observational cohort study. PATIENTS: Eighty consecutive patien...

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Autores principales: Bullock, Martyn, Ren, Yan, O'Neill, Christine, Gill, Anthony, Aniss, Adam, Sywak, Mark, Sidhu, Stan, Delbridge, Leigh, Learoyd, Diana, de Vathaire, Florent, Robinson, Bruce G., Clifton‐Bligh, Roderick J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683578/
https://www.ncbi.nlm.nih.gov/pubmed/26667986
http://dx.doi.org/10.1111/cen.12999
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author Bullock, Martyn
Ren, Yan
O'Neill, Christine
Gill, Anthony
Aniss, Adam
Sywak, Mark
Sidhu, Stan
Delbridge, Leigh
Learoyd, Diana
de Vathaire, Florent
Robinson, Bruce G.
Clifton‐Bligh, Roderick J.
author_facet Bullock, Martyn
Ren, Yan
O'Neill, Christine
Gill, Anthony
Aniss, Adam
Sywak, Mark
Sidhu, Stan
Delbridge, Leigh
Learoyd, Diana
de Vathaire, Florent
Robinson, Bruce G.
Clifton‐Bligh, Roderick J.
author_sort Bullock, Martyn
collection PubMed
description CONTEXT: TERT promoter mutations have been associated with adverse prognosis in papillary thyroid carcinomas (PTCs). OBJECTIVE: We investigated the association between TERT promoter mutations and survival from PTC. DESIGN: Retrospective observational cohort study. PATIENTS: Eighty consecutive patients with PTC who underwent surgery between 1990 and 2003. MEASUREMENTS: TERT promoter was genotyped in DNA from 80 archival PTCs by Sanger sequencing. Median follow‐up was 106 months (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. RESULTS: PTCs 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 = 0·002), male gender (P = 0·01) and Stage IV disease (P = 0·03). Four patients died from PTC during follow‐up: 3 patients with TERT mutations (27%) and one without (1·5%). Disease‐related mortality rate with or without TERT mutations was 33·7 vs 1·6 per 1000 patient‐years respectively, that is 10 (95% CI = 1·0–104·1, P = 0·05) fold higher, after adjustment for age at first surgery and gender. The combination of TERT promoter mutation and BRAF(V) (600E) significantly increased disease‐related death risk (P = 0·002). TERT mutations increased expression of a reporter gene in thyroid cells containing BRAF(V) (600E). CONCLUSIONS: TERT promoter mutations are a major indicator of death due to PTCs. Conversely, absence of TERT mutations portends better survival.
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spelling pubmed-56835782017-11-17 TERT promoter mutations are a major indicator of recurrence and death due to papillary thyroid carcinomas Bullock, Martyn Ren, Yan O'Neill, Christine Gill, Anthony Aniss, Adam Sywak, Mark Sidhu, Stan Delbridge, Leigh Learoyd, Diana de Vathaire, Florent Robinson, Bruce G. Clifton‐Bligh, Roderick J. Clin Endocrinol (Oxf) Original Articles CONTEXT: TERT promoter mutations have been associated with adverse prognosis in papillary thyroid carcinomas (PTCs). OBJECTIVE: We investigated the association between TERT promoter mutations and survival from PTC. DESIGN: Retrospective observational cohort study. PATIENTS: Eighty consecutive patients with PTC who underwent surgery between 1990 and 2003. MEASUREMENTS: TERT promoter was genotyped in DNA from 80 archival PTCs by Sanger sequencing. Median follow‐up was 106 months (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. RESULTS: PTCs 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 = 0·002), male gender (P = 0·01) and Stage IV disease (P = 0·03). Four patients died from PTC during follow‐up: 3 patients with TERT mutations (27%) and one without (1·5%). Disease‐related mortality rate with or without TERT mutations was 33·7 vs 1·6 per 1000 patient‐years respectively, that is 10 (95% CI = 1·0–104·1, P = 0·05) fold higher, after adjustment for age at first surgery and gender. The combination of TERT promoter mutation and BRAF(V) (600E) significantly increased disease‐related death risk (P = 0·002). TERT mutations increased expression of a reporter gene in thyroid cells containing BRAF(V) (600E). CONCLUSIONS: TERT promoter mutations are a major indicator of death due to PTCs. Conversely, absence of TERT mutations portends better survival. John Wiley and Sons Inc. 2016-02-08 2016-08 /pmc/articles/PMC5683578/ /pubmed/26667986 http://dx.doi.org/10.1111/cen.12999 Text en © 2015 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Bullock, Martyn
Ren, Yan
O'Neill, Christine
Gill, Anthony
Aniss, Adam
Sywak, Mark
Sidhu, Stan
Delbridge, Leigh
Learoyd, Diana
de Vathaire, Florent
Robinson, Bruce G.
Clifton‐Bligh, Roderick J.
TERT promoter mutations are a major indicator of recurrence and death due to papillary thyroid carcinomas
title TERT promoter mutations are a major indicator of recurrence and death due to papillary thyroid carcinomas
title_full TERT promoter mutations are a major indicator of recurrence and death due to papillary thyroid carcinomas
title_fullStr TERT promoter mutations are a major indicator of recurrence and death due to papillary thyroid carcinomas
title_full_unstemmed TERT promoter mutations are a major indicator of recurrence and death due to papillary thyroid carcinomas
title_short TERT promoter mutations are a major indicator of recurrence and death due to papillary thyroid carcinomas
title_sort tert promoter mutations are a major indicator of recurrence and death due to papillary thyroid carcinomas
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683578/
https://www.ncbi.nlm.nih.gov/pubmed/26667986
http://dx.doi.org/10.1111/cen.12999
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