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Assessment of BRAFV600E and SMOF412E mutations in epithelial odontogenic tumours

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Tumor Biology


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.

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This work was supported by grants from the National Council for Scientific and Technological Development (CNPq)/Brazil, Coordination for the Improvement of Higher Education Personnel (CAPES)/Brazil and “Fundação de Amparo a Pesquisa do Estado de Minas Gerais” (FAPEMIG)/Brazil. RS Gomez and CC Gomes are research fellows at CNPq/Brazil.

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Correspondence to Ricardo Santiago Gomez.

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Diniz, M.G., Gomes, C.C., Guimarães, B.V.A. et al. Assessment of BRAFV600E and SMOF412E mutations in epithelial odontogenic tumours. Tumor Biol. 36, 5649–5653 (2015).

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