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J Oral Pathol Med. 2019 Feb 9. doi: 10.1111/jop.12839. [Epub ahead of print]

The importance of BRAF-V600E mutation to ameloblastoma metabolism.

Author information

1
Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.
2
Department of Analytical Chemistry, Institute of Chemistry, Universidade Federal da Bahia (UFBA), Salvador, Brazil.
3
Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.

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 were 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 to 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. This article is protected by copyright. All rights reserved.

KEYWORDS:

BRAF ; Ameloblastoma; mass spectrometry; metabolomics; odontogenic tumor

PMID:
30739334
DOI:
10.1111/jop.12839

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