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J Pathol. 2014 Apr;232(5):492-8. doi: 10.1002/path.4317. Epub 2014 Jan 31.

High frequency of BRAF V600E mutations in ameloblastoma.

Author information

1
Department of Medical Biochemistry and Genetics and MediCity Research Laboratories, University of Turku, Finland; Turku Doctoral Programme of Molecular Medicine, Turku, Finland.

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 over-expression 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 of 24 samples, 63%). These data provide novel insight into the poorly understood molecular pathogenesis of ameloblastoma and offer a rationale to test drugs targeting EGFR or mutant BRAF as novel therapies for ameloblastoma.

KEYWORDS:

BRAF; EGFR; ameloblastoma; odontogenic tumour; oncogenic mutation; targeted therapy

PMID:
24374844
PMCID:
PMC4255689
DOI:
10.1002/path.4317
[Indexed for MEDLINE]
Free PMC Article

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