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=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.