Genomic Characterization of Ameloblastoma Subtypes in the Nigerian Population: Toward Precision Surgical Oncology

Ameloblastoma is the most common odontogenic tumor in Nigeria, yet its molecular heterogeneity and the implications of specific genomic alterations for surgical treatment planning and recurrence risk remain poorly understood in African populations. Globally, somatic mutations in BRAF V600E, SMO, and FGFR2 have been identified as drivers of ameloblastoma pathogenesis, but African genomic datasets are underrepresented in published studies. This original PhD study characterizes the genomic landscape of ameloblastoma subtypes in Nigerian patients across three geopolitical zones using next-generation sequencing (NGS) of formalin-fixed paraffin-embedded surgical tissue from confirmed cases at UNTH Enugu, ABUTH Zaria, and LUTH Lagos. One hundred and twenty ameloblastoma specimens were sequenced using a targeted 150-gene cancer panel. Mutation frequencies, copy number variations, and microsatellite instability profiles were analyzed and correlated with histological subtype, anatomical site, clinical stage, surgical margins, and five-year recurrence outcome. Results reveal that BRAF V600E was present in 64.2% of unicystic and conventional ameloblastomas, with a significantly higher prevalence in the South East compared to northern Nigerian specimens, suggesting potential population-level genomic variation. FGFR2 alterations were enriched in desmoplastic subtypes. BRAF-mutant tumors demonstrated a trend toward lower five-year recurrence when resection margins exceeded 1cm. The study pioneers precision oncological stratification of ameloblastoma in Nigeria and proposes a genomic risk-stratification model with implications for personalized surgical planning. Keywords: ameloblastoma, genomics, BRAF V600E, next-generation sequencing, precision oncology.