Activation of telomerase can be observed in almost all human tumor histotypes and detection of the urinary telomeraseactivities is useful for the diagnosis and surveillance of bladder cancer. In this study, we screened, by Sanger sequencing, 302 patients with various urogenital cancers for somatic mutations in the promoter of the telomerasereverse transcriptase (TERT) gene and determined the clinical relevance of TERT promoter mutations in urogenitalcancer. In vitro assays were also performed to evaluate the functional influence of the discovered mutations. We found that the frequencies of somatic mutations in the TERT promoter varied substantially between different types ofurogenital tumors (range: 0-63.7%), with urothelial carcinomas showing the highest mutation frequency and prostate cancer showing no mutation. The mutations upregulated the expression of TERT and enhanced the invasiveness of the tumor cells. The mutations were more prevalent in older patients with invasive diseases and advanced tumor stages, and were associated with significantly shorter survival time. Moreover, we also observed a significant co-occurrence ofmutations between the TERT promoter and the tumor protein 51/retinoblastoma1 (TP53/RB1) signaling pathway. Hence, TERT promoter mutations may serve as important markers for the differential diagnosis and surveillance ofurogenital tumors.

Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.