The <i>Solo</i> Play of <i>TERT</i> Promoter Mutations
The reactivation of telomerase reverse transcriptase (TERT) protein is the principal mechanism of telomere maintenance in cancer cells. Mutations in the <i>TERT</i> promoter (<i>TERTp</i>) are a common mechanism of TERT reactivation in many solid cancers, particularly those o...
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| Format: | Article |
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MDPI AG
2020-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/3/749 |
| _version_ | 1797711844760092672 |
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| author | François Hafezi Danielle Perez Bercoff |
| author_facet | François Hafezi Danielle Perez Bercoff |
| author_sort | François Hafezi |
| collection | DOAJ |
| description | The reactivation of telomerase reverse transcriptase (TERT) protein is the principal mechanism of telomere maintenance in cancer cells. Mutations in the <i>TERT</i> promoter (<i>TERTp</i>) 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 <i>TERTp</i> 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 <i>TERT</i> regulation is crucial when considering its use as a possible target in antitumor strategies. |
| first_indexed | 2024-03-12T07:12:52Z |
| format | Article |
| id | doaj.art-34fbb311b8c44f1e834da0add448bb94 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:12:52Z |
| publishDate | 2020-03-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-34fbb311b8c44f1e834da0add448bb942023-09-02T22:59:11ZengMDPI AGCells2073-44092020-03-019374910.3390/cells9030749cells9030749The <i>Solo</i> Play of <i>TERT</i> Promoter MutationsFrançois Hafezi0Danielle Perez Bercoff1Department of Infection and Immunity, Luxembourg Institute of Health, 29, rue Henri Koch, L-4354 Esch-sur-Alzette, LuxembourgDepartment of Infection and Immunity, Luxembourg Institute of Health, 29, rue Henri Koch, L-4354 Esch-sur-Alzette, LuxembourgThe reactivation of telomerase reverse transcriptase (TERT) protein is the principal mechanism of telomere maintenance in cancer cells. Mutations in the <i>TERT</i> promoter (<i>TERTp</i>) 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 <i>TERTp</i> 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 <i>TERT</i> regulation is crucial when considering its use as a possible target in antitumor strategies.https://www.mdpi.com/2073-4409/9/3/749<i>tert</i> promoter mutationstelomerasecell immortalizationgbm/gliomamelanomathyroid cancerapobec mutationsuv mutations |
| spellingShingle | François Hafezi Danielle Perez Bercoff The <i>Solo</i> Play of <i>TERT</i> Promoter Mutations Cells <i>tert</i> promoter mutations telomerase cell immortalization gbm/glioma melanoma thyroid cancer apobec mutations uv mutations |
| title | The <i>Solo</i> Play of <i>TERT</i> Promoter Mutations |
| title_full | The <i>Solo</i> Play of <i>TERT</i> Promoter Mutations |
| title_fullStr | The <i>Solo</i> Play of <i>TERT</i> Promoter Mutations |
| title_full_unstemmed | The <i>Solo</i> Play of <i>TERT</i> Promoter Mutations |
| title_short | The <i>Solo</i> Play of <i>TERT</i> Promoter Mutations |
| title_sort | i solo i play of i tert i promoter mutations |
| topic | <i>tert</i> promoter mutations telomerase cell immortalization gbm/glioma melanoma thyroid cancer apobec mutations uv mutations |
| url | https://www.mdpi.com/2073-4409/9/3/749 |
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