Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hafezi, François, Perez Bercoff, Danielle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783519044972838912
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
work_keys_str_mv AT hafezifrancois thesoloplayoftertpromotermutations
AT perezbercoffdanielle thesoloplayoftertpromotermutations
AT hafezifrancois soloplayoftertpromotermutations
AT perezbercoffdanielle soloplayoftertpromotermutations