Molecular pathogenesis of ameloblastoma

Area of Science:

• Oral pathology
• Molecular oncology
• Genetics of odontogenic tumors

Background:

• Ameloblastoma (AM) is an aggressive, benign epithelial odontogenic tumor.
• Its exact aetiopathogenesis is not fully understood, despite advances in molecular analysis.
• BRAF p.V600E mutations are frequent but insufficient to explain AM tumorigenesis.

Purpose of the Study:

• To review and integrate current knowledge on AM biology.
• To describe genetic alterations involved in AM pathogenesis.
• To highlight findings from large-scale sequencing and gene expression profiling.

Main Methods:

• Literature review integrating current knowledge on AM biology.
• Focus on large-scale sequencing and gene expression profiling findings.
• Analysis of genetic alterations including mutations and pathway involvement.

Main Results:

• BRAF mutation and MAPK pathway activation are key in AM.
• Alterations in Hedgehog and Wnt/β-catenin pathway genes are implicated.
• Recent reports identify mutations in the KMT2D tumor suppressor gene.

Conclusions:

• Multiple genetic alterations beyond BRAF contribute to AM pathogenesis.
• The biological impact of KMT2D mutations requires further investigation.
• Future research should focus on novel biomarkers for AM diagnosis and targeted therapy.