title: Assessment of BRAFV600E and SMOF412E mutations in epithelial odontogenic tumours.
abstract: The classification of ameloblastoma in multicystic or unicystic variants is associated with its clinical behaviour. Recently, BRAF and SMO mutations have been reported in ameloblastomas. However, it is not clear if such mutations are shared by the multi- and unicystic variants of ameloblastoma or by odontogenic carcinomas. We assessed BRAFV600E and SMOF412E in multicystic, unicystic and desmoplastic ameloblastomas. In addition, we investigated whether the BRAFV600E mutation occurs in odontogenic carcinomas. A total of 28 formalin-fixed paraffin-embedded samples, comprising 17 ameloblastomas and 11 odontogenic carcinomas, were included. The BRAFV600E mutation was assessed by real-time PCR with a specific TaqMan probe and confirmed by Sanger sequencing. The SMOF412E mutation was assessed by Sanger sequencing. Fourteen out of 17 (82 %) ameloblastomas showed the BRAFV600E mutation, specifically, 5/6 (83 %) unicystic, 7/9 (78 %) multicystic and 2/2 desmoplastic ameloblastomas. BRAFV600E mutation was detected in 4/11 (36 %) malignant tumours, specifically, 3/8 (38 %) ameloblastic carcinomas and 1/1 clear cell odontogenic carcinoma, while the two ghost cell odontogenic carcinomas did not harbour this mutation. The SMOF412E mutation was not detected in ameloblastoma. The BRAFV600E-activating mutation is a common event in ameloblastomas, occurring regardless of site or histological type. This mutation is also detected in odontogenic carcinomas. SMO somatic mutation is a secondary genetic event in the ameloblastoma pathogenesis. Our findings support the possibility for personalised, molecular-targeted therapy for ameloblastomas and odontogenic carcinomas harbouring the BRAFV600E mutation.
authors: Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte, MG, 31270-901, Brazil.
authors: Marina Gonçalves
authors: MG
authors: Diniz
authors: Carolina Cavalieri
authors: CC
authors: Gomes
authors: Bruna Viana Antonini
authors: BV
authors: Guimarães
authors: Wagner Henriques
authors: WH
authors: Castro
authors: Júlio César Tanos
authors: JC
authors: Lacerda
authors: Sergio Vitorino
authors: SV
authors: Cardoso
authors: Paulo Rogério
authors: PR
authors: de Faria
authors: Fernando Luiz
authors: FL
authors: Dias
authors: Ana Lúcia Amaral
authors: AL
authors: Eisenberg
authors: Adriano Mota
authors: AM
authors: Loyola
authors: Ricardo Santiago
authors: RS
authors: Gomez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000564:Ameloblastoma / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D009808:Odontogenic Tumors / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D000072086:Smoothened Receptor
chemical_list: D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf