The telomerase reverse transcriptase (TERT) promoter mutations are associated with increased TERT mRNA and TERT protein levels, telomerase activity, and shorter but stable telomere length. TERT promoter mutation is the most common mutation that occurs in approximately 60-80% of bladder cancer patients. The TERT promoter mutations occur in a wide spectrum of urothelial lesions, including benign urothelial proliferation and tumor-like conditions, benign urothelial tumors, premalignant and putative precursor lesions, urothelial carcinoma and its variants, and non-urothelial malignancies. The prevalence and incidence of TERT promoter mutations in a total of 7,259 cases from the urinary tract were systematically reviewed. Different platforms of TERT promoter mutation detection were presented. In this review, we also discussed the significance and clinical implications of TERT promoter mutation detection in urothelial tumorigenesis, surveillance and early detection, diagnosis, differential diagnosis, prognosis, prediction of treatment responses and clinical outcome. Identification of TERT promoter mutations from urine or plasma cell-free DNA (liquid biopsy) will facilitate bladder cancer screening program and optimal clinical management. A better understanding of TERT promoter mutation and its pathway would open new therapeutic avenues for bladder cancer patients.
Human pathology. 2022 Jun 11 [Epub ahead of print]
Liang Cheng, Shaobo Zhang, Mingsheng Wang, Antonio Lopez-Beltran
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN; Department of Urology, Indiana University School of Medicine, Indianapolis, IN. Electronic address: ., Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN., Department of Morphological Sciences, University of Cordoba Medical School, Cordoba, Spain.