Comprehensive genetic profiling of malignant odontogenic tumors in a Japanese cohort using multi-gene panel testing

Malignant odontogenic tumors (MOTs) are exceedingly rare neoplasms for which no standard treatment has been established. To the best of our knowledge, no comprehensive genomic profiling (CGP) of MOTs using real-world data has been reported in Japan. In this study, we analyzed the CGP data from Japanese patients with MOTs to identify potential therapeutic targets. We collected clinical and genomic data of patients with MOTs (n=11) who had CGP tests performed under the national health insurance scheme from June 2019 to February 2025, using the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database. The 11 MOTs enrolled represented 0.012% of all malignancies in the C-CAT database. The most frequent alteration in MOTs was CDKN2A (45.5%), followed by CDKN2B (36.4%), BRAF (27.3%), and BCOR and SMO (18.2%). All patients with BRAF mutations were diagnosed with either ameloblastic carcinoma or metastasizing ameloblastoma, and all shared the common V600E mutation. A fusion of the EWSR1 gene was detected in 3 patients. They had EWSR1- CREB1 , EWSR1- ATF1 and EWSR1- CREM , respectively. This study elucidates the genomic characteristics of MOTs in Japanese patients. The findings may aid in identifying novel therapeutic targets and offer insights for developing personalized treatment strategies.