TERT Promoter Mutations in Primary and Recurrent Bladder Cancer - Expert Commentary

Point mutations in telomerase reverse transcriptase (TERT) promotor are reported in invasive and noninvasive, primary and recurrent urothelial bladder cancer (UBC). A deeper understanding of the clinical correlates of TERT promoter mutations is critical for designing early detection tools for predicting outcomes in UBC patients.

A recent paper published by Roggisch et al. in Urologic Oncology examined the status of TERT promoter mutation in different UBC stages, assessed its clinical significance in patients, and compared the mutations identified in primary UBC to those in recurrent tumors. The investigators included 75 UBC patients, including 25 muscle-invasive bladder cancer (MIBC) and 50 non-muscle invasive bladder cancer (NMIBC) patients. 21 NMIBC patients developed recurrence. The researchers used Sanger sequencing to analyze the TERT promoter mutations in UBC.

The study found a high prevalence of 63/75 (84%) of TERT promoter mutations in UBC patients. TERT promoter mutations were present in 80% (20/25) of MIBC and 86% (43/50) of NMIBC samples. The investigators found discordant TERT promoter mutational status in 9.5% (2/21) of patients. TERT promoter mutational status did not significantly correlate with overall survival; however, this analysis was limited by the sample size of the study.

Defining the specific effects of various TERT promoter mutations on telomere length and replicative immortality of cancer cells and their impact on the clinical course of the disease is needed for precision medicine strategies that target UBC patients with TERT promoter mutations.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York

Reference: 

1. Roggisch, Jenny, Thorsten Ecke, and Stefan Koch. "Molecular identification of telomerase reverse transcriptase (TERT) promotor mutations in primary and recurrent tumors of invasive and noninvasive urothelial bladder cancer." In Urologic Oncology: Seminars and Original Investigations. Elsevier, 2019.

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