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
Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, Padova, Italy.
Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology (IOV), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padova, Italy.
Front Oncol. 2021 Nov 10;11:782658. doi: 10.3389/fonc.2021.782658. eCollection 2021.
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 () gene and the impact of TERT single nucleotide polymorphism (SNP) rs2853669 in patients surgically treated for OCSCC.
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.
Forty-five tumours harboured 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 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.
-124 C>T 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.
迄今为止，对于口腔鳞状细胞癌（OCSCC）患者尚无有用的预后生物标志物，该肿瘤具有不确定的生物学行为及随后不可预测的临床病程。我们旨在研究端粒酶逆转录酶（TERT）基因启动子区域两个复发性体细胞突变（-124 C>T和-146 C>T）的预后意义，以及TERT单核苷酸多态性（SNP）rs2853669对接受手术治疗的OCSCC患者的影响。
对144例肿瘤组织和57例来自OCSCC患者的正常相邻黏膜（AM）标本，研究rs2853669、-124 C>T和-146 C>T的基因频率以及端粒长度。
45例肿瘤存在TERT启动子突变（31.3%），其中-124 C>T和-146 C>T分别占改变的64.4%和35.6%。携带-124 C>T TERT启动子突变肿瘤的患者，其AM中的端粒最短（p=0.016），并且局部复发风险更高（风险比[HR]：2.75，p=0.0143）、死亡风险更高（HR：2.71，p=0.0079）以及疾病进展风险更高（HR：2.71，p=0.0024），rs2853669的T/T基因型同时存在会增强这种影响。
-124 C>T TERT启动子突变以及rs2853669 SNP的T/T基因型是接受手术治疗的OCSCC患者中有吸引力的独立预后生物标志物，这些基因变异的共存对疾病的侵袭性具有协同影响。
