LAUSR

Background: Genetic and epigenetic alterations are both important in tumorigenesis. However, their association in oral carcinogenesis has not been fully investigated yet. In this study, we analyzed somatic mutations of tumor-related genes and promoter methylation of tumor-suppressor genes (TSGs) in oral malignancies/premalignancies, and analyzed their association. Materials and Methods: 39 oral squamous cell carcinomas (OSCCs) and 2 oral epithelial dysplasias (OEDs) were obtained as fresh-frozen?. Somatic mutations of 46 tumor-related genes, 13 TSGs and 33 oncogenes, were analyzed by targeted next-generation sequencing (NGS). Promoter methylation of five TSG: (p16/INK4A, CMTM3, EGFLAM, NKX2-3, and RBP4) were determined by methylation-specific PCR (MSP). Results: Somatic mutations of tumor-related genes were observed in 63.4% of 41 OSCCs/OEDs. Particularly, mutations of p53 and PIK3CA were observed 39.0% and 31.7%, respectively, of the 41 OSCCs/OEDs. Promoter methylation of p16/INK4A, CMTM3, NKX2-3, RBP4, and EGFLAM were observed in 34.1%, 48.8%, 41.5%, 68.3%, and 36.6%, respectively, of the 41 OSCCs/OEDs. No differences in the frequency of promoter methylation of the five genes were observed between tumors with and without somatic mutations of p53 and PIK3CA. Conclusions: Promoter methylation was observed at high frequencies regardless of mutation status of p53 and PIK3CA in OSCCs/OEDs. Oral tumorigenesis appears to be difficult to be explained solely by genetic events indicating involvement of epigenetic events. Citation Format: Masanobu Abe, Kazuto Hoshi, Toshikazu Ushijima. Promoter methylation occurs at high frequencies regardless of mutation status of tumor-associated genes in oral malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6005.