Occurrence, functionality and abundance of the TERT promoter mutations

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F21%3A00547097" target="_blank" >RIV/68378041:_____/21:00547097 - isvavai.cz</a>

Result on the web

<a href="https://onlinelibrary.wiley.com/doi/10.1002/ijc.33750" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/ijc.33750</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ijc.33750" target="_blank" >10.1002/ijc.33750</a>

Result language

angličtina

Original language name

Occurrence, functionality and abundance of the TERT promoter mutations

Original language description

Telomere shortening at chromosomal ends due to the constraints of the DNA replication process acts as a tumor suppressor by restricting the replicative potential in primary cells. Cancers evade that limitation primarily through the reactivation of telomerase via different mechanisms. Mutations within the promoter of the telomerase reverse transcriptase (TERT) gene represent a definite mechanism for the ribonucleic enzyme regeneration predominantly in cancers that arise from tissues with low rates of self-renewal. The promoter mutations cause a moderate increase in TERT transcription and consequent telomerase upregulation to the levels sufficient to delay replicative senescence but not prevent bulk telomere shortening and genomic instability. Since the discovery, a staggering number of studies have resolved the discrete aspects, effects and clinical relevance of the TERT promoter mutations. The promoter mutations link transcription of TERT with oncogenic pathways, associate with markers of poor outcome and define patients with reduced survivals in several cancers. In this review, we discuss the occurrence and impact of the promoter mutations and highlight the mechanism of TERT activation. We further deliberate on the foundational question of the abundance of the TERT promoter mutations and a general dearth of functional mutations within noncoding sequences, as evident from pan-cancer analysis of the whole-genomes. We posit that the favorable genomic constellation within the TERT promoter may be less than a common occurrence in other noncoding functional elements. Besides, the evolutionary constraints limit the functional fraction within the human genome, hence the lack of abundant mutations outside the coding sequences.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International Journal of Cancer

ISSN

0020-7136

e-ISSN

1097-0215

Volume of the periodical

149

Issue of the periodical within the volume

11

Country of publishing house

DE - GERMANY

Number of pages

11

Pages from-to

1852-1862

UT code for WoS article

000680921900001

EID of the result in the Scopus database

2-s2.0-85111735787