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The Solo Play of TERT Promoter Mutations
The reactivation of telomerase reverse transcriptase (TERT) protein is the principal mechanism of telomere maintenance in cancer cells. Mutations in the TERT promoter (TERTp) are a common mechanism of TERT reactivation in many solid cancers, particularly those originating from slow-replicating tissu...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140675/ https://www.ncbi.nlm.nih.gov/pubmed/32204305 http://dx.doi.org/10.3390/cells9030749 |
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author | Hafezi, François Perez Bercoff, Danielle |
author_facet | Hafezi, François Perez Bercoff, Danielle |
author_sort | Hafezi, François |
collection | PubMed |
description | The reactivation of telomerase reverse transcriptase (TERT) protein is the principal mechanism of telomere maintenance in cancer cells. Mutations in the TERT promoter (TERTp) are a common mechanism of TERT reactivation in many solid cancers, particularly those originating from slow-replicating tissues. They are associated with increased TERT levels, telomere stabilization, and cell immortalization and proliferation. Much effort has been invested in recent years in characterizing their prevalence in different cancers and their potential as biomarkers for tumor stratification, as well as assessing their molecular mechanism of action, but much remains to be understood. Notably, they appear late in cell transformation and are mutually exclusive with each other as well as with other telomere maintenance mechanisms, indicative of overlapping selective advantages and of a strict regulation of TERT expression levels. In this review, we summarized the latest literature on the role and prevalence of TERTp mutations across different cancer types, highlighting their biased distribution. We then discussed the need to maintain TERT levels at sufficient levels to immortalize cells and promote proliferation while remaining within cell sustainability levels. A better understanding of TERT regulation is crucial when considering its use as a possible target in antitumor strategies. |
format | Online Article Text |
id | pubmed-7140675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71406752020-04-13 The Solo Play of TERT Promoter Mutations Hafezi, François Perez Bercoff, Danielle Cells Review The reactivation of telomerase reverse transcriptase (TERT) protein is the principal mechanism of telomere maintenance in cancer cells. Mutations in the TERT promoter (TERTp) are a common mechanism of TERT reactivation in many solid cancers, particularly those originating from slow-replicating tissues. They are associated with increased TERT levels, telomere stabilization, and cell immortalization and proliferation. Much effort has been invested in recent years in characterizing their prevalence in different cancers and their potential as biomarkers for tumor stratification, as well as assessing their molecular mechanism of action, but much remains to be understood. Notably, they appear late in cell transformation and are mutually exclusive with each other as well as with other telomere maintenance mechanisms, indicative of overlapping selective advantages and of a strict regulation of TERT expression levels. In this review, we summarized the latest literature on the role and prevalence of TERTp mutations across different cancer types, highlighting their biased distribution. We then discussed the need to maintain TERT levels at sufficient levels to immortalize cells and promote proliferation while remaining within cell sustainability levels. A better understanding of TERT regulation is crucial when considering its use as a possible target in antitumor strategies. MDPI 2020-03-19 /pmc/articles/PMC7140675/ /pubmed/32204305 http://dx.doi.org/10.3390/cells9030749 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Hafezi, François Perez Bercoff, Danielle The Solo Play of TERT Promoter Mutations |
title | The Solo Play of TERT Promoter Mutations |
title_full | The Solo Play of TERT Promoter Mutations |
title_fullStr | The Solo Play of TERT Promoter Mutations |
title_full_unstemmed | The Solo Play of TERT Promoter Mutations |
title_short | The Solo Play of TERT Promoter Mutations |
title_sort | solo play of tert promoter mutations |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140675/ https://www.ncbi.nlm.nih.gov/pubmed/32204305 http://dx.doi.org/10.3390/cells9030749 |
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