TERTPromoter Mutation C228T Increases Risk for Tumor Recurrence and Death in Head and Neck Cancer Patients

Background:Head and neck squamous cell carcinoma (HNSCC) is usually associated to tobacco and alcohol consumption. Increased telomerase activity has been consistently detected in 80-90% of malignant tumors, including HNSCC. Mutations within the promoter region of telomerase reverse transcriptase (TERT) that confer enhancedTERTpromoter activity have been reported in two major hotspots, designated C228T and C250T. Objectives:To evaluateTERTpromoter mutations C228T and C250T in HNSCC patients from Brazil and correlate with patients' outcome. Materials and Methods:Formalin-fixed paraffin-embedded tissues were obtained from 88 HNSCC patients and analyzed forTERTpromoter mutations C228T and C250T by pyrosequencing. Results:The overall prevalence of hotspotTERTmutations in HNSCC samples was of 27.3%, with 6.8% at locus C228T and 20.5% at C250T. The majority (92%) of mutated cases were located in oral cavity, mainly at the tongue. We observed that 94.4% of the patients harboringTERTpromoter mutation C250T were alcohol consumers (p= 0.032) and 66.7% of the patients harboringTERTpromoter mutation C228T were not alcohol consumers (p= 0.035). The presence of C228T mutation impacted patient outcome, with a significant decrease in disease-free survival (20.0 vs. 63.0%,p=0.017) and in overall survival (16.7 vs. 45.1%,p= 0.017). Conclusion:This is the first report of aTERTpromoter mutations in HNSCC patients from South America. The high prevalence ofTERTmutation, as well as its association with poor disease-free survival and overall survival, particular at C228T locus might serve as a prognostic biomarker in HNSCC to help clinicians in the management of treatment.