Frequent oncogenic BRAF V600E mutation in odontogenic keratocyst

Odontogenic keratocyst (OKC), also known as keratocystic odontogenic tumor (KCOT), has clinical significance due to its high incidence as well as high recurrence rate after surgical enucleation. Current clinical management for OCK is entirely dependent on surgical approach. While various genetic alterations, such as PTCH1 mutation and loss of heterozygosity in tumor suppressor genes, have been reported, the molecular background of OKC is not well-understood. Although recent identification of BRAF V600E mutation and subsequent activation of mitogen-activated protein kinase (MAPK) pathway in ameloblastoma and odontogenic tumors provide additional options with targeted therapeutics, the molecular background of OKC is not well understood.

In this study, we examined BRAF V600E mutation from paraffin embedded OKC samples by tumor cell enriched microdissection and TA cloning of amplified DNA. We further examined the relationship between BRAF V600E mutation and clinical parameters.

We found frequent BRAF V600E mutation in OKC (24 of 38 samples, 63.2%). However, BRAF V600E mutational status is not related with clinical indexes such as size, location, and recurrence. In orthokeratinized odontogenic cyst, there is one case of BRAF 600E mutation from 11 samples (9.1%).

These results indicate that BRAF V600E mutation occurs in OKCs at a high rate and plays an important role in the pathogenesis of OKCs.