Absence of BRAFV600E mutation in odontogenic keratocysts.

Background: Mutations in the patched 1 (PTCH1) gene are the main genetic alteration reported in sporadic and nevoid basal cell carcinoma-associated odontogenic keratocyst (OKC). Oncogenic mutations, including BRAFV600E, previously considered exclusive of malignant neoplasms have been reported in odontogenic tumors. Recently, a high frequency of BRAFV600E mutation has been reported in OKC. Because of the considerable recurrence rate of OKC, the identification of druggable genetic mutations can be relevant in the management of extensive lesions.

Methods: A set of 28 OKCs was included in this work. Initially, 10 sporadic and eight OKC samples from four NBCCS patients (a pair of lesions from each syndromic patient) were submitted to targeted next-generation sequencing (NGS) of 2800 different mutations in 50 oncogenes and tumor suppressor genes, including BRAF. Ten extra sporadic OKC samples were included to assess BRAFV600E mutation using TaqMan allele-specific qPCR.

Results: The following missense mutations occurred in one case each: ATM p.Ser333Phe, SMO p.Gly416Glu, PIK3CA p.Ser326Phe, FBXW7 p.Ser438Phe, JAK2 p.Ser605Phe, PTEN p.Arg173His, ATM p.Cys353Arg, PTEN p.Ser294Arg, MET p.His1112Tyr. None of the 18 samples showed the BRAFV600E (or any other V600) mutation in the NGS. BRAFV600E mutation was detected by qPCR in one of the 10 OKC. Collectively, our results show BRAFV600E mutation in 1 of 28 OKC cases.

Conclusion: On the basis of our results, OKCs do not present recurrent hotspot mutations in these 50 genes commonly mutated in cancer. In addition, BRAFV600E does not play a central role in OKC pathogenesis.