The importance of BRAF-V600E mutation to ameloblastoma metabolism.

Abstract

BACKGROUND:

Ameloblastoma is a locally infiltrative, aggressive epithelial odontogenic neoplasm. BRAF-V600E mutation is frequently found in this tumor and has a pivotal role in its pathogenesis, but the consequences of this alteration need to be addressed. An untargeted metabolomics approach was applied to verify whether metabolic disturbances are related to tumor biology and whether BRAF-V600E mutation contributes to these alterations.

METHODS:

Formalin-fixed and paraffin-embedded tissue specimens from thirteen ameloblastoma and six dental follicles were included in this study. BRAF mutational status was determined by competitive allele-specific real-time PCR. Metabolite extracts were analyzed using gas chromatography coupled to mass spectrometry. Univariate and multivariate statistical methods were employed to compare the metabolic profiles of the samples.

RESULTS:

The abundance of eleven metabolites was significantly higher in ameloblastoma in relation to dental follicles, including amino acids, fatty acids, carbohydrates, inorganic acids, and organoheterocyclic compounds. The presence of BRAF-V600E mutations in ameloblastoma was related to decreased levels of glycerol in comparison with tumors carrying only wild-type alleles of this gene. No metabolic differences were observed between recurrent and primary manifestations of ameloblastoma.

CONCLUSIONS:

Ameloblastoma exhibits a distinct metabolic profile from normal odontogenic epithelium. BRAF-V600E may contribute to metabolic alterations in ameloblastoma. Collectively, our findings suggest that metabolic alterations might play a role in tumor pathogenesis.

• Authors: Filipe Fideles Duarte-Andrade, André Myller Barbosa Silva, Jéssica Gardone Vitório, Gisele André Baptista Canuto, Sara Ferreira Santos Costa, Marina Gonçalves Diniz, Ana Paula Fernandes, Juliano Simões de Toledo, Leiliane Coelho André, Carolina Cavaliéri Gomes, Ricardo Santiago Gomez, Felipe Paiva Fonseca
• Journal: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology (J Oral Pathol Med) Vol. 48 Issue 4 Pg. 307-314 (Apr 2019) ISSN: 1600-0714 [Electronic] Denmark
• PMID: 30739334 (Publication Type: Journal Article)
• Copyright: © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• BRAF protein, human
• Proto-Oncogene Proteins B-raf

Topics

• Alleles
• Ameloblastoma (genetics, metabolism)
• DNA Mutational Analysis
• Humans
• Mutation
• Odontogenic Tumors (genetics, metabolism)
• Proto-Oncogene Proteins B-raf (genetics)