Mutational Landscape of Ameloblastoma: Analysis of BRAF and Other Key Mutations in Chinese Patients.

Objectives: To investigate the prevalence of BRAF, SMO, KRAS, HRAS, NRAS, FGRF2, and CTNNB1 gene mutations in Chinese ameloblastoma (AM) patients and explore their associations with clinical characteristics.

Materials and methods: DNA was extracted from 89 formalin-fixed paraffin-embedded AM samples (9 unicystic and 80 conventional). PCR and Sanger sequencing were used to detect mutations, followed by statistical analysis to assess correlations between mutations and clinical variables.

Results: BRAF V600E mutations were significantly prevalent, occurring in 92% (59/64) of mandibular AMs compared to 40% (10/25) in maxillary AMs. SMO mutations were found in 20% (5/25) of maxillary and 3.1% (2/64) of mandibular AMs. FGFR2 mutations were detected in six maxillary and two mandibular AMs, while RAS mutations were present in four maxillary and one mandibular AM. No detectable HRAS, NRAS(G12), or CTNNB1 mutations were observed. BRAF mutations showed mutual exclusivity with SMO and FGFR2 mutations.

Conclusion: The high prevalence of BRAF V600E mutations, particularly in mandibular AMs, suggests its potential as a diagnostic and therapeutic target. Distinct mutation profiles between maxillary and mandibular AMs indicate molecular diversity. In BRAF-negative cases, alternative oncogenic pathways involving SMO, FGFR2, and RAS may be actionable targets, underscoring the need for personalized treatment approaches.