Differences in BRAF V600E mutation between the epithelium and mesenchyme in classic ameloblastoma

Abstract

Objective: Laser capture microdissection (LCM) was used to pinpoint the mutated tissue in ameloblastoma and investigate whether B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation is the main pathogenic gene in classic ameloblastoma.

Study design: A total of 24 patients with ameloblastoma scheduled to undergo surgery between 2000 and 2024 were included in the study. LCM was used to isolate tumor cells. Oxford nanopore technology (ONT) was used to analyze the collected cells. GO and KEGG enrichment analyses were then performed on the 300 most highly expressed genes in the epithelial tissue and mesenchyme.

Results: Mandibular follicular ameloblastoma showed BRAF V600E mutations in all epithelial cells but not in the mesenchyme. The mutation rate was significantly higher in mandibular ameloblastomas compared to the maxilla (P < .05). RNA-seq showed that traditional follicular ameloblastoma epithelium was enriched in "growth factor receptor binding" and "angiogenesis regulation," while the mesenchyme was enriched in "ECM receptor interaction." KEGG enrichment analysis showed differential gene expression, mainly in MAPK and PI3K-AKT pathways.

Conclusion: Classical follicular ameloblastoma shows the presence of BRAF V600E mutation in epithelial tissue, with a higher mutation rate in the mandible than in the maxilla. The signaling pathways of MAPK and PI3K may be significantly involved in epithelial signal transduction.