The investigation of new mutations in telomerase reverse transcriptase promoter region in association with bladder cancer

Year 2025, Volume: 29 Issue: 6, 2230 - 2238, 02.11.2025

Hanan Ramadhan , Safaa Abdulabass Alhamedi Ammar Ihsan Awadh Omar Farooq Abdul-Rasheed Safaa Mezban

https://doi.org/10.12991/jrespharm.1796220

Abstract

Telomerase reverse transcriptase (TERT) is frequently reactivated in Urothelial Bladder Cancer (UBC) due to changes in its promoter region, rendering it a vital target for cancer-specific genetic modifications. The present work was aimed to investigate the TERT promoter region to explore the mutations that may affect the incidence and the pathogenesis of Urothelial Bladder Cancer in a study included 59 patients subjected to either transurethral bladder resection or radical cystectomy from which serum and tissue samples were obtained and the DNA extraction was performed with the use of purification Promega kit and the amplified DNA samples were sequenced by Sanger sequencing using an automated DNA sequencer to determine TERT gene promoter mutations. The results of the study showed that 47 patients out of 59 showed a mutation at the position -129 (1295233), 44 of them with c.232_233insA and 3 patients with a C233A mutation. Sixteen patients of the 59 patients subjected to the genetic analysis showed a mutation at the position -109 (1295213) in the TERT promoter region, the later mutation showed to be associated significantly with the grade of the reaction wheras the former mutation didn’t show that. On the other hand the two novel mutation showed a non-significant association with the levels of hTERT, age, gender, muscle invasiveness, recurrence and smoking and it was concluded from that the mutation in the TERT promoter region my have an effect on the TERT expression that participate in the bladder cancer pathogenisis which need further studies.

Keywords

TERT promoter mutation , Bladder cancer , Cancer genetics , Somatic mutation , Telomerase reverse transcriptase

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