AUTHOR=Arantes Lidia Maria Rebolho Batista , Cruvinel-Carloni Adriana , de Carvalho Ana Carolina , Sorroche Bruna Pereira , Carvalho André Lopes , Scapulatempo-Neto Cristovam , Reis Rui Manuel 

TITLE=TERT Promoter Mutation C228T Increases Risk for Tumor Recurrence and Death in Head and Neck Cancer Patients

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01275

DOI=10.3389/fonc.2020.01275

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> 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 (<italic>TERT</italic>) that confer enhanced <italic>TERT</italic> promoter activity have been reported in two major hotspots, designated C228T and C250T.</p><p><bold>Objectives:</bold> To evaluate <italic>TERT</italic> promoter mutations C228T and C250T in HNSCC patients from Brazil and correlate with patients' outcome.</p><p><bold>Materials and Methods:</bold> Formalin-fixed paraffin-embedded tissues were obtained from 88 HNSCC patients and analyzed for <italic>TERT</italic> promoter mutations C228T and C250T by pyrosequencing.</p><p><bold>Results:</bold> The overall prevalence of hotspot <italic>TERT</italic> mutations 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 harboring <italic>TERT</italic> promoter mutation C250T were alcohol consumers (<italic>p</italic> = 0.032) and 66.7% of the patients harboring <italic>TERT</italic> promoter mutation C228T were not alcohol consumers (<italic>p</italic> = 0.035). The presence of C228T mutation impacted patient outcome, with a significant decrease in disease-free survival (20.0 vs. 63.0%, <italic>p</italic> =0.017) and in overall survival (16.7 vs. 45.1%, <italic>p</italic> = 0.017).</p><p><bold>Conclusion:</bold> This is the first report of a <italic>TERT</italic> promoter mutations in HNSCC patients from South America. The high prevalence of <italic>TERT</italic> mutation, 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.</p>