Understanding TERT promoter mutations: a common path to immortality
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/45048 |
Resumo: | Telomerase (TERT) activation is a fundamental step in tumorigenesis. By maintaining telomere length, telomerase relieves a main barrier on cellular lifespan, enabling limitless proliferation driven by oncogenes. The recently discovered, highly recurrent mutations in the promoter of TERT are found in over 50 cancer types, and are the most common mutation in many cancers. Transcriptional activation of TERT, via promoter mutation or other mechanisms, is the rate-limiting step in production of active telomerase. Although TERT is expressed in stem cells, it is naturally silenced upon differentiation. Thus, the presence of TERT promoter mutations may shed light on whether a particular tumor arose from a stem cell or more differentiated cell type. It is becoming clear that TERT mutations occur early during cellular transformation, and activate the TERT promoter by recruiting transcription factors that do not normally regulate TERT gene expression. This review highlights the fundamental and widespread role of TERT promoter mutations in tumorigenesis, including recent progress on their mechanism of transcriptional activation. These somatic promoter mutations, along with germline variation in the TERT locus also appear to have significant value as biomarkers of patient outcome. Understanding the precise molecular mechanism of TERT activation by promoter mutation and germline variation may inspire novel cancer cell-specific targeted therapies for a large number of cancer patients. |
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Understanding TERT promoter mutations: a common path to immortalityScience & TechnologyTelomerase (TERT) activation is a fundamental step in tumorigenesis. By maintaining telomere length, telomerase relieves a main barrier on cellular lifespan, enabling limitless proliferation driven by oncogenes. The recently discovered, highly recurrent mutations in the promoter of TERT are found in over 50 cancer types, and are the most common mutation in many cancers. Transcriptional activation of TERT, via promoter mutation or other mechanisms, is the rate-limiting step in production of active telomerase. Although TERT is expressed in stem cells, it is naturally silenced upon differentiation. Thus, the presence of TERT promoter mutations may shed light on whether a particular tumor arose from a stem cell or more differentiated cell type. It is becoming clear that TERT mutations occur early during cellular transformation, and activate the TERT promoter by recruiting transcription factors that do not normally regulate TERT gene expression. This review highlights the fundamental and widespread role of TERT promoter mutations in tumorigenesis, including recent progress on their mechanism of transcriptional activation. These somatic promoter mutations, along with germline variation in the TERT locus also appear to have significant value as biomarkers of patient outcome. Understanding the precise molecular mechanism of TERT activation by promoter mutation and germline variation may inspire novel cancer cell-specific targeted therapies for a large number of cancer patients.Support was provided from a generous gift from the Dabbiere family(RJB,AM,JFC), the Hana Jabsheh Research Initiative (RJB,AM,JFC), and NIH grants NCI P50CA097257 (RJB,AM,JFC), P01CA118816-06 (RJB,AM,JFC), R01HG003008 (HTR), and R01CA163336 (JSS). Additional support was provided from the Sontag Foundation Distinguished Scientist Award (JSS), Fundação para a Ciência e Tecnologia SFRH/BD/88220/2012 (AXM), IF/00601/2012 (BMC), Programa Operacional Regional do Norte (ON.2—O Novo Norte) (BMC), Quadro de Referência Estratégico Nacional (BMC), and Fundo Europeu de Desenvolvimento Regional (BMC).info:eu-repo/semantics/publishedVersionAmerican Association for Cancer ResearchUniversidade do MinhoBell, Robert J. A.Rube, H. TomasMagalhães, Ana XavierCosta, Bruno MarquesMancini, AndrewSong, Jun S.Costello, Joseph F.2016-04-032016-04-03T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/45048engBell, R. J. A., Rube, H. T., Xavier-Magalhães, A., Costa, B. M., Mancini, A., Song, J. S., & Costello, J. F. (2016). Understanding TERT promoter mutations: A common path to immortality. [Review]. Molecular Cancer Research, 14(4), 315-323. doi: 10.1158/1541-7786.mcr-16-00031541-778610.1158/1541-7786.MCR-16-000326941407http://mcr.aacrjournals.orginfo: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:RCAAP2023-07-21T12:05:35Zoai:repositorium.sdum.uminho.pt:1822/45048Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:56:03.696268Repositório 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 |
Understanding TERT promoter mutations: a common path to immortality |
title |
Understanding TERT promoter mutations: a common path to immortality |
spellingShingle |
Understanding TERT promoter mutations: a common path to immortality Bell, Robert J. A. Science & Technology |
title_short |
Understanding TERT promoter mutations: a common path to immortality |
title_full |
Understanding TERT promoter mutations: a common path to immortality |
title_fullStr |
Understanding TERT promoter mutations: a common path to immortality |
title_full_unstemmed |
Understanding TERT promoter mutations: a common path to immortality |
title_sort |
Understanding TERT promoter mutations: a common path to immortality |
author |
Bell, Robert J. A. |
author_facet |
Bell, Robert J. A. Rube, H. Tomas Magalhães, Ana Xavier Costa, Bruno Marques Mancini, Andrew Song, Jun S. Costello, Joseph F. |
author_role |
author |
author2 |
Rube, H. Tomas Magalhães, Ana Xavier Costa, Bruno Marques Mancini, Andrew Song, Jun S. Costello, Joseph F. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Bell, Robert J. A. Rube, H. Tomas Magalhães, Ana Xavier Costa, Bruno Marques Mancini, Andrew Song, Jun S. Costello, Joseph F. |
dc.subject.por.fl_str_mv |
Science & Technology |
topic |
Science & Technology |
description |
Telomerase (TERT) activation is a fundamental step in tumorigenesis. By maintaining telomere length, telomerase relieves a main barrier on cellular lifespan, enabling limitless proliferation driven by oncogenes. The recently discovered, highly recurrent mutations in the promoter of TERT are found in over 50 cancer types, and are the most common mutation in many cancers. Transcriptional activation of TERT, via promoter mutation or other mechanisms, is the rate-limiting step in production of active telomerase. Although TERT is expressed in stem cells, it is naturally silenced upon differentiation. Thus, the presence of TERT promoter mutations may shed light on whether a particular tumor arose from a stem cell or more differentiated cell type. It is becoming clear that TERT mutations occur early during cellular transformation, and activate the TERT promoter by recruiting transcription factors that do not normally regulate TERT gene expression. This review highlights the fundamental and widespread role of TERT promoter mutations in tumorigenesis, including recent progress on their mechanism of transcriptional activation. These somatic promoter mutations, along with germline variation in the TERT locus also appear to have significant value as biomarkers of patient outcome. Understanding the precise molecular mechanism of TERT activation by promoter mutation and germline variation may inspire novel cancer cell-specific targeted therapies for a large number of cancer patients. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-04-03 2016-04-03T00:00:00Z |
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/1822/45048 |
url |
http://hdl.handle.net/1822/45048 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Bell, R. J. A., Rube, H. T., Xavier-Magalhães, A., Costa, B. M., Mancini, A., Song, J. S., & Costello, J. F. (2016). Understanding TERT promoter mutations: A common path to immortality. [Review]. Molecular Cancer Research, 14(4), 315-323. doi: 10.1158/1541-7786.mcr-16-0003 1541-7786 10.1158/1541-7786.MCR-16-0003 26941407 http://mcr.aacrjournals.org |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
American Association for Cancer Research |
publisher.none.fl_str_mv |
American Association for Cancer Research |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132347088502784 |