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The importance of BRAF‐V600E mutation to ameloblastoma metabolism
Author(s) -
DuarteAndrade Filipe Fideles,
Silva André Myller Barbosa,
Vitório Jéssica Gardone,
Canuto Gisele André Baptista,
Costa Sara Ferreira Santos,
Diniz Marina Gonçalves,
Fernandes Ana Paula,
Toledo Juliano Simões,
André Leiliane Coelho,
Gomes Carolina Cavaliéri,
Gomez Ricardo Santiago,
Fonseca Felipe Paiva
Publication year - 2019
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12839
Subject(s) - ameloblastoma , pathogenesis , odontogenic tumor , biology , mutation , pathology , metabolite , cancer research , gene , odontogenic , genetics , medicine , endocrinology , immunology , maxilla , anatomy
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.