1. TERT Promoter Mutations and rs2853669 Polymorphism: Useful Markers for Clinical Outcome Stratification of Patients With Oral Cavity Squamous Cell Carcinoma
- Author
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Silvia Giunco, Paolo Boscolo-Rizzo, Enrica Rampazzo, Giancarlo Tirelli, Lara Alessandrini, Roberto Di Carlo, Marco Rossi, Piero Nicolai, Anna Menegaldo, Valentina Carraro, Margherita Tofanelli, Luigia Bandolin, Giacomo Spinato, Enzo Emanuelli, Monica Mantovani, Marco Stellin, Rossana Bussani, Angelo Paolo Dei Tos, Maria Guido, Marzia Morello, Jonathan Fussey, Giovanni Esposito, Jerry Polesel, and Anita De Rossi
- Subjects
oral cavity squamous cell carcinoma (OCSCC) ,telomerase ,TERT promoter mutations ,SNP rs2853669 ,telomere ,prognostic biomarkers ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
ObjectiveTo date, no useful prognostic biomarker exists for patients with oral squamous cell carcinoma (OCSCC), a tumour with uncertain biological behaviour and subsequent unpredictable clinical course. We aim to investigate the prognostic significance of two recurrent somatic mutations (-124 C>T and -146 C>T) within the promoter of telomerase reverse transcriptase (TERT) gene and the impact of TERT single nucleotide polymorphism (SNP) rs2853669 in patients surgically treated for OCSCC.MethodsThe genetic frequencies of rs2853669, -124 C>T and -146 C>T as well as the telomere length were investigated in 144 tumours and 57 normal adjacent mucosal (AM) specimens from OCSCC patients.ResultsForty-five tumours harboured TERT promoter mutations (31.3%), with -124 C>T and -146 C>T accounting for 64.4% and 35.6% of the alterations respectively. Patients with -124 C>T TERT promoter mutated tumours had the shortest telomeres in the AM (p=0.016) and showed higher risk of local recurrence (hazard ratio [HR]:2.75, p=0.0143), death (HR:2.71, p=0.0079) and disease progression (HR:2.71, p=0.0024) with the effect being potentiated by the co-occurrence of T/T genotype of rs2853669.Conclusion-124 C>T TERT promoter mutation as well as the T/T genotype of the rs2853669 SNP are attractive independent prognostic biomarkers in patients surgically treated for OCSCC, with the coexistence of these genetic variants showing a synergistic impact on the aggressiveness of the disease.
- Published
- 2021
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