Evaluation of TERT promoter mutations in tumor biopsies and urine sediment of Moroccan bladder cancer patients

Abstract

Background: Human telomerase reverse transcriptase (hTERT) promoter mutations are common genetic events in blad- der cancer (BC) and have been recognized as potential biomarkers for BC diagnosis and prognosis. Detection of TERT promoter mutations as urine-based tests has previously been reported to detect primary and recurrent BC. This study was planned to evaluate hTERT promoter mutations in both biopsies and urines from BC patients to assess the interest and the usefulness of introducing these biomarkers for better management of BC in Morocco. Methods: In a cohort study involving a series of BC 70 patients with different stages and grades, hTERT promoter mutations were identified in both fresh biopsies and urine sediments by PCR amplification and DNA sequencing. Results: Overall, hTERT promoter mutations were reported in 60% of cancer biopsies (42/70), the hotspot mutations C228T and C250T were respectively identified in 80.95% (34/42) and 16.67% (7/42) of positive cases. Other mutations: A161C and G149T were also reported and were obtained in 2.38% (1/42) and 2.38% (1/42), respectively. hTERT promoter mutations were identified in 30% of matched urine sediments (21/70) and showed an overall sensitivity of 50% and specificity of 100%. In patients with non-muscle invasive bladder cancer, no statistically significant association was detected between TERT promoter mutations and recurrence-free survival (HR: 1.224, 95% CI: 0.373–4.011, p = 0.739), and overall survival (HR: 0.363, 95% CI: 0.041–3.244, p = 0.364). Conclusion: hTERT promoter mutations are early events occurring with high frequencies and can be identified in the exfo- liated cells, making them an interesting non-invasive biomarker for diagnosis and follow-up of bladder cancer.