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Implications of TERT promoter mutations and telomerase activity in urothelial carcinogenesis

Nature Reviews Urology volume 15, pages 386–393 (2018)Cite this article

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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) tumours 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 UCBs, 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. TERT promoter mutations could arise during regeneration of normal urothelium and, owing to consequential telomerase reactivation, might be the basis of UCB initiation, which represents a new model of urothelial cancer origination. In the future, TERT promoter mutations and telomerase activity might have diagnostic and therapeutic applications in UCB.

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Fig. 1: Classical concept of telomere and telomerase functions in tumour suppression and initiation.
Fig. 2: Alternative concept of telomere and telomerase functions in tumour suppression and initiation.
Fig. 3: The cell of origin of cancer in urothelial carcinoma of the bladder.

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Authors and Affiliations

  1. Department of Urology, University of Ulm, Ulm, Germany

    Cagatay Günes, Felix Wezel & Christian Bolenz

  2. Department of Biology, Jack Birch Unit of Molecular Carcinogenesis, University of York, York, UK

    Jennifer Southgate

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Günes, C., Wezel, F., Southgate, J. et al. Implications of TERT promoter mutations and telomerase activity in urothelial carcinogenesis. Nat Rev Urol 15, 386–393 (2018). https://doi.org/10.1038/s41585-018-0001-5

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