BRAF p.V600E Mutation in Mixed Odontogenic Tumors and Its Clinical Correlation: A Systematic Review and Meta-Analysis

Abstract

The impact of BRAF p.V600E mutation on the pathogenesis of mixed odontogenic tumors remains uncertain. We conducted a systematic review and meta-analysis to determine the prevalence of BRAF mutation in mixed odontogenic tumors and to evaluate the correlation between this mutation and the clinical characteristics of these lesions. The study protocol was registered in PROSPERO (registration number CRD42025636575). A comprehensive search of the PubMed/MEDLINE, Embase, and Scopus databases was conducted. The study population included patients diagnosed with ameloblastic fibroma (AF), developing odontoma (DO), ameloblastic fibro-odontoma (AFO), ameloblastic fibro-dentinoma (AFD), odontoma (OD), odontogenic sarcoma (OS), or ameloblastic fibrosarcoma (AFS), with BRAF mutation detection results. The AFO, AFD, and DO were categorized in 1 group for further analysis. The study quality was assessed using the modified scale of the Agency for Healthcare Research and Quality for observational studies. A random-effects meta-analysis model was employed using Review Manager software. Statistical heterogeneity was assessed by forest plots, Tau-squared, Cochrane Chi-square, and I² statistics. A total of 9 studies were included in the analysis. Overall, AFS demonstrated the highest BRAF mutation prevalence (71.4%), followed by AF (67.4%) and AFO/AFD/DO (55.6%), respectively. No OD cases exhibited this mutation. In addition, AF, AFO/AFD/DO, and AFS lesions exhibited significantly larger average sizes compared to OD. AFS demonstrated significantly higher recurrence rates than AFO/AFD/DO and OD. Additionally, a significant female predilection for BRAF-mutated AF was identified. BRAF mutation is associated with AF, AFO/AFD/DO, and AFS, but not OD. Its presence in a substantial portion of AFO/AFD/DO, together with their larger size compared to OD, could support a neoplastic nature in at least a subset of these lesions, though a hamartomatous DO may exist. Further investigation and clinical correlation remain essential to distinguish these entities.