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Implications of TERT promoter mutations and telomerase activity for urothelial carcinogenesis

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JournalNature reviews. Urology
DateAccepted/In press - 14 Feb 2017
DateE-pub ahead of print (current) - 29 Mar 2018
Early online date29/03/18
Original languageEnglish

Abstract

Telomerase activity imparts eukaryotic cells with unlimited proliferation capacity, one of the cancer hallmarks. Over 90% of human urothelial carcinoma of the bladder (UCB) are positive for telomerase activity. Telomerase activation can occur through several mechanisms. Mutations in the core promoter region of the human telomerase reverse transcriptase gene (TERT) cause telomerase reactivation in 60-80% of UCB, whereas the prevalence of these mutations is lower in urothelial cancers of other origins. TERT promoter mutations are the
most frequent genetic alteration across all stages of UCB, indicating a strong selection pressure during neoplastic transformation.[Au:We avoid formulations referring to the article authors (“we”) in the abstract. I have edited the following text accordingly, OK?] TERT [Au:”promoter”?] promoter mutations could arise during regeneration of normal urothelium[Au:I tried to simplify here; is this what you meant?] and due to consequential telomerase reactivation, might be the basis of UCB initiation, which represents a new model for the origination of urothelial carcinogenesis. In the future, TERT promoter mutations and
telomerase activity might have diagnostic and therapeutic applications in UCB.

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