High frequency of BRAF V600E mutations in ameloblastoma
Authors
Kari J. Kurppa, Javier Catón, Peter R. Morgan, Ari Ristimäki, Blandine Ruhin, Jari Kellokoski, Klaus Elenius, and Kristiina Heikinheimo
Institution
Uni Turku
Country
Finland
Year
2014
Journal
J Pathol
Abstract
Ameloblastoma is a benign but locally infiltrative odontogenic neoplasm. Although
ameloblastomas rarely metastasise, recurrences together with radical surgery often result in
facial deformity and significant morbidity. Development of non-invasive therapies has been
precluded by a lack of understanding of the molecular background of ameloblastoma
pathogenesis. When addressing the role of ERBB receptors as potential new targets for
ameloblastoma we discovered significant EGFR overexpression in clinical samples using
real-time RT-PCR but observed variable sensitivity of novel primary ameloblastoma cells to
EGFR-targeted drugs in vitro. In the quest for mutations downstream of EGFR that could
explain this apparent discrepancy, Sanger sequencing revealed an oncogenic BRAF V600E
mutation in the cell line resistant to EGFR inhibition. Further analysis of the clinical samples
by Sanger sequencing and BRAF V600E-specific immunohistochemistry demonstrated a
high frequency of BRAF V600E mutations (15 out of 24 samples, 63%). These data provide
novel insight into the poorly understood molecular pathogenesis of ameloblastoma and offer
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a rationale to test drugs targeting EGFR or mutant BRAF as novel therapies for
ameloblastoma.
Keywords: Ameloblastoma, BRAF, EGFR, odontogenic tumour, oncogenic mutation,
targeted therapy