TERT promoter mutation positive oral cavity carcinomas, a clinically and genetically distinct subgroup of head and neck squamous cell carcinomas

Backgrounds: The importance of TERT promoter (pTERT) mutation of oral cavity squamous cell carcinoma (OCSCC) with clinical features and genetic alterations are not well recognized.

Methods: We retrospectively analyzed genetic data from multiple databases, including 260 cases from the C-CAT database, 407 cases from the MSK-MetTropism database, and 40 OCSCC datasets from in-house clinical samples.

Results: From C-CAT database, TP53 (66%), CDKN2A (51%), and pTERT (29%) were the most frequent mutations observed. pTERT mutations were more prevalent in OCSCC (63%), younger individuals, and women (46%), with lower rates of alcohol abuse and smoking and co-mutated with TP53, HRAS, and CASP8. MSK-MetTroposim data validated with the enrichment of pTERT mutations in OCSCC, among women and Asian individuals. In-house datasets OCSCC with pTERT mutation (50%) characterized by fewer recurrent neck metastases.

Conclusion: The study suggests that OCSCC with pTERT mutation represents a distinct subgroup with unique clinical and genetic characteristics.