Implications of TERT promoter mutations and telomerase activity for urothelial carcinogenesis

Cagatay Gunes; Felix Wezel; Jennifer Southgate; Christian Bolenz

doi:10.1038/s41585-018-0001-5

Implications of TERT promoter mutations and telomerase activity for urothelial carcinogenesis

Cagatay Gunes, Felix Wezel, Jennifer Southgate, Christian Bolenz

Jack Birch Unit

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	Nature reviews. Urology
Early online date	29 Mar 2018
DOIs	https://doi.org/10.1038/s41585-018-0001-5
Publication status	E-pub ahead of print - 29 Mar 2018

Bibliographical note

© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

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Cite this

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title = "Implications of TERT promoter mutations and telomerase activity for urothelial carcinogenesis",

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 themost 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 andtelomerase activity might have diagnostic and therapeutic applications in UCB.",

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AU - Bolenz, Christian

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