Activating Telomerase TERT Promoter Mutations and Their Application for the Detection of Bladder Cancer.

This review summarizes state-of-the-art knowledge in early-generation and novel urine biomarkers targeting the telomerase pathway for the detection and follow-up of bladder cancer (BC). The limitations of the assays detecting telomerase reactivation are discussed and the potential of transcription-activating mutations in the promoter of the TERT gene detected in the urine as promising simple non-invasive BC biomarkers is highlighted. Studies have shown good sensitivity and specificity of the urinary TERT promoter mutations in case-control studies and, more recently, in a pilot prospective cohort study, where the marker was detected up to 10 years prior to clinical diagnosis. However, large prospective cohort studies and intervention studies are required to fully validate their robustness and assess their clinical utility. Furthermore, it may be interesting to evaluate whether the clinical performance of urinary TERT promoter mutations could increase when combined with other simple urinary biomarkers. Finally, different approaches for assessment of TERT promoter mutations in urine samples are presented together with technical challenges, thus highlighting the need of careful technological validation and standardization of laboratory methods prior to translation into clinical practice.

International journal of molecular sciences. 2020 Aug 21*** epublish ***

Maria Zvereva, Eduard Pisarev, Ismail Hosen, Olga Kisil, Simon Matskeplishvili, Elena Kubareva, David Kamalov, Alexander Tivtikyan, Arnaud Manel, Emmanuel Vian, Armais Kamalov, Thorsten Ecke, Florence Le Calvez-Kelm

Chair of Chemistry of Natural Compounds, Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia., Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia., Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, University of Dhaka, Dhaka 1000, Bangladesh., Gause Institute of New Antibiotics, 119021 Moscow, Russia., Medical Research and Education Center, Lomonosov Moscow State University, 119992 Moscow, Russia., Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119992 Moscow, Russia., Le Creusot Hospital, 71200 Le Creusot, France., Department of Urology, Protestant Clinic of Lyon, 69300 Lyon, France., Department of Urology, HELIOS Hospital Bad Saarow, D-15526 Bad Saarow, Germany., International Agency for Research on Cancer (IARC), 69372 Lyon, France.