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The Solo Play of TERT Promoter Mutations

Department of Infection and Immunity, Luxembourg Institute of Health, 29, rue Henri Koch, L-4354 Esch-sur-Alzette, Luxembourg
Author to whom correspondence should be addressed.
Cells 2020, 9(3), 749;
Received: 11 February 2020 / Revised: 16 March 2020 / Accepted: 16 March 2020 / Published: 19 March 2020
(This article belongs to the Section Cell Signaling and Regulated Cell Death)
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. View Full-Text
Keywords: TERT promoter mutations; telomerase; cell immortalization; GBM/glioma; melanoma; thyroid cancer; APOBEC mutations; UV mutations TERT promoter mutations; telomerase; cell immortalization; GBM/glioma; melanoma; thyroid cancer; APOBEC mutations; UV mutations
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Hafezi, F.; Perez Bercoff, D. The Solo Play of TERT Promoter Mutations. Cells 2020, 9, 749.

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