Prevalence of BRAF V600E mutations in ameloblastomas seen at the largest tertiary care centre in Sub-Saharan Africa

Abstract

Ameloblastoma, the most common odontogenic tumour in Sub-Saharan Africa, poses considerable clinical challenges due to its locally aggressive behaviour and high recurrence rate. Recent molecular advances have identified BRAF V600E mutations as pivotal in tumorigenesis, alongside mutations in other MAPK pathway genes and SMO mutations in the hedgehog pathway. These discoveries suggest potential targets for emerging therapies, including BRAF and MEK inhibitors, which have demonstrated efficacy in preclinical studies for limiting tumour growth. Standard treatment involves disfiguring surgical excision, with an emphasis on wide local resection to minimize recurrence, though challenges persist in achieving clear margins due to its infiltrative nature. Alternative therapies targeting specific mutations offer promising avenues for less invasive management, pending further clinical validation to establish their efficacy and safety. This study investigated 56 ameloblastomas from a single Oral Health Centre in the Western Cape using BRAF VE1 immunohistochemical staining and ARMS-PCR on all cases, and Sanger sequencing on 11 randomly selected cases. PCR identified BRAF V600E mutations in 89.3% of cases, with mandibular ameloblastomas demonstrating a higher prevalence (95.9%) compared to maxillary cases (42.9%). This disparity underscores the need for much larger future research to elucidate causative mutations and explore potential molecular targeted therapies to improve outcomes in managing this challenging tumour type.