Počet záznamů: 1
Occurrence, functionality and abundance of the TERT promoter mutations
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SYSNO ASEP 0547097 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Occurrence, functionality and abundance of the TERT promoter mutations Tvůrce(i) Rachakonda, S. (DE)
Jörg, D.H. (DE)
Kumar, Rajiv (UEM-P)Zdroj.dok. International Journal of Cancer. - : Wiley - ISSN 0020-7136
Roč. 149, č. 11 (2021), s. 1852-1862Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. DE - Německo Klíč. slova cancers ; telomerase ; telomeres ; TERT promoter mutations Obor OECD Cell biology Způsob publikování Open access Institucionální podpora UEM-P - RVO:68378041 UT WOS 000680921900001 EID SCOPUS 85111735787 DOI 10.1002/ijc.33750 Anotace 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. Pracoviště Ústav experimentální medicíny Kontakt Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Rok sběru 2022 Elektronická adresa https://onlinelibrary.wiley.com/doi/10.1002/ijc.33750
Počet záznamů: 1