TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas

Detalhes bibliográficos
Autor(a) principal: Melo, Miguel
Data de Publicação: 2014
Outros Autores: Da Rocha, Adriana Gaspar, Vinagre, João, Batista, Rui, Peixoto, Joana, Tavares, Catarina, Celestino, Ricardo, Almeida, Ana, Salgado, Catarina, Eloy, Catarina, Castro, Patrícia, Prazeres, Hugo, Lima, Jorge, Amaro, Teresina, Lobo, Cláudia, Martins, Maria João, Moura, Margarida, Cavaco, Branca, Leite, Valeriano, Cameselle-Teijeiro, José Manuel, Carrilho, Francisco, Carvalheiro, Manuela, Máximo, Valdemar, Sobrinho-Simões, Manuel, Soares, Paula
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/149673
Resumo: Funding: This study was supported by the Portuguese Foundation for Science and Technology through PhD Grant SFRH/BD/81940/ 2011 (to J.V.); PhD Grant SFRH/BD/87887/2012 (to C.T.); PhD Grant SFRH/BD/79135/2011 (to A.A.); and the Scientific Investigation Project PIC/IC/83037/2007. Further funding was obtained from the project “Microenvironment, Metabolism and Cancer,” partially supported by Programa Operacional Regional do Norte (ON.2-O Novo Norte), under the Quadro de Referência Estratégico Nacional, and through the European Regional Development Fund. The work of J.M.C.-T. was supported by Grant PI12/00749-FEDER from the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness (Madrid, Spain). The Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) is an associate laboratory of the Portuguese Ministry of Science, Technology, and Higher Education, which is partially supported by the Foundation for Science and Technology.
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spelling TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomasEndocrinology, Diabetes and MetabolismBiochemistryEndocrinologyClinical BiochemistryBiochemistry, medicalSDG 3 - Good Health and Well-beingFunding: This study was supported by the Portuguese Foundation for Science and Technology through PhD Grant SFRH/BD/81940/ 2011 (to J.V.); PhD Grant SFRH/BD/87887/2012 (to C.T.); PhD Grant SFRH/BD/79135/2011 (to A.A.); and the Scientific Investigation Project PIC/IC/83037/2007. Further funding was obtained from the project “Microenvironment, Metabolism and Cancer,” partially supported by Programa Operacional Regional do Norte (ON.2-O Novo Norte), under the Quadro de Referência Estratégico Nacional, and through the European Regional Development Fund. The work of J.M.C.-T. was supported by Grant PI12/00749-FEDER from the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness (Madrid, Spain). The Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) is an associate laboratory of the Portuguese Ministry of Science, Technology, and Higher Education, which is partially supported by the Foundation for Science and Technology.Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives:Weaimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P< .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P=.001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P=.001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01-53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36-415.76; P = .03) in PTCs. Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNMelo, MiguelDa Rocha, Adriana GasparVinagre, JoãoBatista, RuiPeixoto, JoanaTavares, CatarinaCelestino, RicardoAlmeida, AnaSalgado, CatarinaEloy, CatarinaCastro, PatríciaPrazeres, HugoLima, JorgeAmaro, TeresinaLobo, CláudiaMartins, Maria JoãoMoura, MargaridaCavaco, BrancaLeite, ValerianoCameselle-Teijeiro, José ManuelCarrilho, FranciscoCarvalheiro, ManuelaMáximo, ValdemarSobrinho-Simões, ManuelSoares, Paula2023-02-24T22:24:42Z2014-052014-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/149673eng0021-972XPURE: 49089092https://doi.org/10.1210/jc.2013-3734info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:31:33Zoai:run.unl.pt:10362/149673Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:53:49.750168Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas
title TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas
spellingShingle TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas
Melo, Miguel
Endocrinology, Diabetes and Metabolism
Biochemistry
Endocrinology
Clinical Biochemistry
Biochemistry, medical
SDG 3 - Good Health and Well-being
title_short TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas
title_full TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas
title_fullStr TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas
title_full_unstemmed TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas
title_sort TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas
author Melo, Miguel
author_facet Melo, Miguel
Da Rocha, Adriana Gaspar
Vinagre, João
Batista, Rui
Peixoto, Joana
Tavares, Catarina
Celestino, Ricardo
Almeida, Ana
Salgado, Catarina
Eloy, Catarina
Castro, Patrícia
Prazeres, Hugo
Lima, Jorge
Amaro, Teresina
Lobo, Cláudia
Martins, Maria João
Moura, Margarida
Cavaco, Branca
Leite, Valeriano
Cameselle-Teijeiro, José Manuel
Carrilho, Francisco
Carvalheiro, Manuela
Máximo, Valdemar
Sobrinho-Simões, Manuel
Soares, Paula
author_role author
author2 Da Rocha, Adriana Gaspar
Vinagre, João
Batista, Rui
Peixoto, Joana
Tavares, Catarina
Celestino, Ricardo
Almeida, Ana
Salgado, Catarina
Eloy, Catarina
Castro, Patrícia
Prazeres, Hugo
Lima, Jorge
Amaro, Teresina
Lobo, Cláudia
Martins, Maria João
Moura, Margarida
Cavaco, Branca
Leite, Valeriano
Cameselle-Teijeiro, José Manuel
Carrilho, Francisco
Carvalheiro, Manuela
Máximo, Valdemar
Sobrinho-Simões, Manuel
Soares, Paula
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Melo, Miguel
Da Rocha, Adriana Gaspar
Vinagre, João
Batista, Rui
Peixoto, Joana
Tavares, Catarina
Celestino, Ricardo
Almeida, Ana
Salgado, Catarina
Eloy, Catarina
Castro, Patrícia
Prazeres, Hugo
Lima, Jorge
Amaro, Teresina
Lobo, Cláudia
Martins, Maria João
Moura, Margarida
Cavaco, Branca
Leite, Valeriano
Cameselle-Teijeiro, José Manuel
Carrilho, Francisco
Carvalheiro, Manuela
Máximo, Valdemar
Sobrinho-Simões, Manuel
Soares, Paula
dc.subject.por.fl_str_mv Endocrinology, Diabetes and Metabolism
Biochemistry
Endocrinology
Clinical Biochemistry
Biochemistry, medical
SDG 3 - Good Health and Well-being
topic Endocrinology, Diabetes and Metabolism
Biochemistry
Endocrinology
Clinical Biochemistry
Biochemistry, medical
SDG 3 - Good Health and Well-being
description Funding: This study was supported by the Portuguese Foundation for Science and Technology through PhD Grant SFRH/BD/81940/ 2011 (to J.V.); PhD Grant SFRH/BD/87887/2012 (to C.T.); PhD Grant SFRH/BD/79135/2011 (to A.A.); and the Scientific Investigation Project PIC/IC/83037/2007. Further funding was obtained from the project “Microenvironment, Metabolism and Cancer,” partially supported by Programa Operacional Regional do Norte (ON.2-O Novo Norte), under the Quadro de Referência Estratégico Nacional, and through the European Regional Development Fund. The work of J.M.C.-T. was supported by Grant PI12/00749-FEDER from the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness (Madrid, Spain). The Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) is an associate laboratory of the Portuguese Ministry of Science, Technology, and Higher Education, which is partially supported by the Foundation for Science and Technology.
publishDate 2014
dc.date.none.fl_str_mv 2014-05
2014-05-01T00:00:00Z
2023-02-24T22:24:42Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/149673
url http://hdl.handle.net/10362/149673
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0021-972X
PURE: 49089092
https://doi.org/10.1210/jc.2013-3734
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instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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