TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes

Detalhes bibliográficos
Autor(a) principal: Vinagre, João
Data de Publicação: 2016
Outros Autores: Nabais, Joana, Pinheiro, Jorge, Batista, Rui, Oliveira, Rui Caetano, Gonçalves, António Pedro, Pestana, Ana, Reis, Marta, Mesquita, Bárbara, Pinto, Vasco, Lyra, Joana, Cipriano, Maria Augusta, Ferreira, Miguel Godinho, Lopes, José Manuel, 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/10400.7/681
Resumo: One of the hallmarks of cancer is its unlimited replicative potential that needs a compensatory mechanism for the consequential telomere erosion. Telomerase promoter (TERTp) mutations were recently reported as a novel mechanism for telomerase re-activation/expression in order to maintain telomere length. Pancreatic endocrine tumors (PETs) were so far recognized to rely mainly on the alternative lengthening of telomeres (ALT) mechanism. It was our objective to study if TERTp mutations were present in pancreatic endocrine tumors (PET) and could represent an alternative mechanism to ALT. TERTp mutations were detected in 7% of the cases studied and were mainly associated to patients harbouring hereditary syndromes. In vitro, using PET-derived cell lines and by luciferase reporter assay, these mutations confer a 2 to 4-fold increase in telomerase transcription activity. These novel alterations are able to recruit ETS transcription factor members, in particular GABP-α and ETV1, to the newly generated binding sites. We report for the first time TERTp mutations in PETs and PET-derived cell lines. Additionally, our data indicate that these mutations serve as an alternative mechanism and in an exclusive manner to ALT, in particular in patients with hereditary syndromes.
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spelling TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromesNeuroendocrine cancerTelomeresOne of the hallmarks of cancer is its unlimited replicative potential that needs a compensatory mechanism for the consequential telomere erosion. Telomerase promoter (TERTp) mutations were recently reported as a novel mechanism for telomerase re-activation/expression in order to maintain telomere length. Pancreatic endocrine tumors (PETs) were so far recognized to rely mainly on the alternative lengthening of telomeres (ALT) mechanism. It was our objective to study if TERTp mutations were present in pancreatic endocrine tumors (PET) and could represent an alternative mechanism to ALT. TERTp mutations were detected in 7% of the cases studied and were mainly associated to patients harbouring hereditary syndromes. In vitro, using PET-derived cell lines and by luciferase reporter assay, these mutations confer a 2 to 4-fold increase in telomerase transcription activity. These novel alterations are able to recruit ETS transcription factor members, in particular GABP-α and ETV1, to the newly generated binding sites. We report for the first time TERTp mutations in PETs and PET-derived cell lines. Additionally, our data indicate that these mutations serve as an alternative mechanism and in an exclusive manner to ALT, in particular in patients with hereditary syndromes.Fundação para a Ciência e a Tecnologia; Norte 2020 – Programa Operacional Regional do Norte project: (“Advancing cancer research: from basic knowledgment to application” - grant: NORTE-01-0145-FEDER-000029); Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education: (I3S).Nature Publishing GroupARCAVinagre, JoãoNabais, JoanaPinheiro, JorgeBatista, RuiOliveira, Rui CaetanoGonçalves, António PedroPestana, AnaReis, MartaMesquita, BárbaraPinto, VascoLyra, JoanaCipriano, Maria AugustaFerreira, Miguel GodinhoLopes, José ManuelSobrinho-Simões, ManuelSoares, Paula2016-07-20T15:15:02Z2016-07-142016-07-14T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/mswordhttp://hdl.handle.net/10400.7/681engVinagre, J. et al. TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes. Sci. Rep. 6, 29714; doi: 10.1038/ srep29714 (2016).10.1038/srep29714info: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:RCAAP2022-11-29T14:35:04Zoai:arca.igc.gulbenkian.pt:10400.7/681Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T16:11:55.039571Repositório 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 in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes
title TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes
spellingShingle TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes
Vinagre, João
Neuroendocrine cancer
Telomeres
title_short TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes
title_full TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes
title_fullStr TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes
title_full_unstemmed TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes
title_sort TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes
author Vinagre, João
author_facet Vinagre, João
Nabais, Joana
Pinheiro, Jorge
Batista, Rui
Oliveira, Rui Caetano
Gonçalves, António Pedro
Pestana, Ana
Reis, Marta
Mesquita, Bárbara
Pinto, Vasco
Lyra, Joana
Cipriano, Maria Augusta
Ferreira, Miguel Godinho
Lopes, José Manuel
Sobrinho-Simões, Manuel
Soares, Paula
author_role author
author2 Nabais, Joana
Pinheiro, Jorge
Batista, Rui
Oliveira, Rui Caetano
Gonçalves, António Pedro
Pestana, Ana
Reis, Marta
Mesquita, Bárbara
Pinto, Vasco
Lyra, Joana
Cipriano, Maria Augusta
Ferreira, Miguel Godinho
Lopes, José Manuel
Sobrinho-Simões, Manuel
Soares, Paula
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv ARCA
dc.contributor.author.fl_str_mv Vinagre, João
Nabais, Joana
Pinheiro, Jorge
Batista, Rui
Oliveira, Rui Caetano
Gonçalves, António Pedro
Pestana, Ana
Reis, Marta
Mesquita, Bárbara
Pinto, Vasco
Lyra, Joana
Cipriano, Maria Augusta
Ferreira, Miguel Godinho
Lopes, José Manuel
Sobrinho-Simões, Manuel
Soares, Paula
dc.subject.por.fl_str_mv Neuroendocrine cancer
Telomeres
topic Neuroendocrine cancer
Telomeres
description One of the hallmarks of cancer is its unlimited replicative potential that needs a compensatory mechanism for the consequential telomere erosion. Telomerase promoter (TERTp) mutations were recently reported as a novel mechanism for telomerase re-activation/expression in order to maintain telomere length. Pancreatic endocrine tumors (PETs) were so far recognized to rely mainly on the alternative lengthening of telomeres (ALT) mechanism. It was our objective to study if TERTp mutations were present in pancreatic endocrine tumors (PET) and could represent an alternative mechanism to ALT. TERTp mutations were detected in 7% of the cases studied and were mainly associated to patients harbouring hereditary syndromes. In vitro, using PET-derived cell lines and by luciferase reporter assay, these mutations confer a 2 to 4-fold increase in telomerase transcription activity. These novel alterations are able to recruit ETS transcription factor members, in particular GABP-α and ETV1, to the newly generated binding sites. We report for the first time TERTp mutations in PETs and PET-derived cell lines. Additionally, our data indicate that these mutations serve as an alternative mechanism and in an exclusive manner to ALT, in particular in patients with hereditary syndromes.
publishDate 2016
dc.date.none.fl_str_mv 2016-07-20T15:15:02Z
2016-07-14
2016-07-14T00:00:00Z
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/10400.7/681
url http://hdl.handle.net/10400.7/681
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Vinagre, J. et al. TERT promoter mutations in pancreatic endocrine tumours are rare and mainly found in tumours from patients with hereditary syndromes. Sci. Rep. 6, 29714; doi: 10.1038/ srep29714 (2016).
10.1038/srep29714
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/msword
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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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