TERT Promoter Mutations and rs2853669 Polymorphism: Useful Markers for Clinical Outcome Stratification of Patients With Oral Cavity Squamous Cell Carcinoma

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; Anita De Rossi

doi:10.3389/fonc.2021.782658

TERT Promoter Mutations and rs2853669 Polymorphism: Useful Markers for Clinical Outcome Stratification of Patients With Oral Cavity Squamous Cell Carcinoma

Front Oncol. 2021 Nov 10:11:782658. doi: 10.3389/fonc.2021.782658. eCollection 2021.

Authors

Silvia Giunco^{1

2}, Paolo Boscolo-Rizzo^{3

4}, Enrica Rampazzo¹, Giancarlo Tirelli⁴, Lara Alessandrini⁵, Roberto Di Carlo⁶, Marco Rossi⁷, Piero Nicolai⁶, Anna Menegaldo³, Valentina Carraro⁵, Margherita Tofanelli⁴, Luigia Bandolin⁶, Giacomo Spinato^{1

3}, Enzo Emanuelli³, Monica Mantovani³, Marco Stellin³, Rossana Bussani⁸, Angelo Paolo Dei Tos⁵, Maria Guido⁹, Marzia Morello², Jonathan Fussey¹⁰, Giovanni Esposito², Jerry Polesel¹¹, Anita De Rossi^{1

2}

Affiliations

¹ Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, Padova, Italy.
² Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology (IOV), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padova, Italy.
³ Department of Neurosciences, Section of Otolaryngology, University of Padova, Treviso, Italy.
⁴ Department of Medical, Surgical and Health Sciences, Section of Otolaryngology, University of Trieste, Trieste, Italy.
⁵ Department of Medicine (DIMED), Section of Pathology, University of Padova, Padova, Italy.
⁶ Department of Neurosciences, Section of Otolaryngology, University of Padova, Padova, Italy.
⁷ Unit of Oral and Maxillofacial Surgery, Treviso Regional Hospital, Treviso, Italy.
⁸ Department of Medical, Surgical and Health Sciences, Section of Pathology, University of Trieste, Trieste, Italy.
⁹ Department of Medicine (DIMED), Section of Pathology, University of Padova, Treviso, Italy.
¹⁰ Department of ENT/Head and Neck Surgery, Queen Elizabeth University Hospital Birmingham, Birmingham, United Kingdom.
¹¹ Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy.

Abstract

Objective: To 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.

Methods: The 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.

Results: Forty-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.

Keywords: SNP rs2853669; TERT promoter mutations; oral cavity squamous cell carcinoma (OCSCC); prognostic biomarkers; survival; telomerase; telomere.

Copyright © 2021 Giunco, Boscolo-Rizzo, Rampazzo, Tirelli, Alessandrini, Di Carlo, Rossi, Nicolai, Menegaldo, Carraro, Tofanelli, Bandolin, Spinato, Emanuelli, Mantovani, Stellin, Bussani, Dei Tos, Guido, Morello, Fussey, Esposito, Polesel and De Rossi.