AUTHOR=Giunco Silvia , Boscolo-Rizzo Paolo , Rampazzo Enrica , Tirelli Giancarlo , Alessandrini Lara , Di Carlo Roberto , Rossi Marco , Nicolai Piero , Menegaldo Anna , Carraro Valentina , Tofanelli Margherita , Bandolin Luigia , Spinato Giacomo , Emanuelli Enzo , Mantovani Monica , Stellin Marco , Bussani Rossana , Dei Tos Angelo Paolo , Guido Maria , Morello Marzia , Fussey Jonathan , Esposito Giovanni , Polesel Jerry , De Rossi Anita TITLE=TERT Promoter Mutations and rs2853669 Polymorphism: Useful Markers for Clinical Outcome Stratification of Patients With Oral Cavity Squamous Cell Carcinoma JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.782658 DOI=10.3389/fonc.2021.782658 ISSN=2234-943X 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.