Telomerase reverse transcriptase gene promoter mutations help discern the origin of urogenital tumors: a genomic and molecular study

Eur Urol. 2014 Feb;65(2):274-7. doi: 10.1016/j.eururo.2013.10.038. Epub 2013 Nov 5.


Activation of telomerase can be observed in almost all human tumor histotypes and detection of the urinary telomerase activities 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 telomerase reverse transcriptase (TERT) gene and determined the clinical relevance of TERT promoter mutations in urogenital cancer. 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 of urogenital 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 of mutations 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 of urogenital tumors.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Lineage / genetics*
  • DNA Mutational Analysis*
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Testing / methods*
  • Humans
  • Mutation*
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Predictive Value of Tests
  • Promoter Regions, Genetic*
  • Retinoblastoma Protein / genetics
  • Risk Factors
  • Telomerase / genetics*
  • Tumor Suppressor Protein p53 / genetics
  • Urogenital Neoplasms / enzymology*
  • Urogenital Neoplasms / genetics*
  • Urogenital Neoplasms / pathology


  • Retinoblastoma Protein
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • TERT protein, human
  • Telomerase