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.

Assessing pathogenic mutations in dental follicles as an attempt to identify early events in odontogenic tumours tumourigenesis.

OBJECTIVE: Driver oncogenic mutations have been reported in several benign neoplasms. While ameloblastomas show BRAF p.V600E mutations, adenomatoid odontogenic tumours harbour either KRAS p.G12R or p.G12 V. The lack of understanding of the core molecular changes involved in tumour initiation and progression represents a critical barrier to developing new strategies for cancer detection and prevention. Considering the fact that ameloblastoma and adenomatoid odontogenic tumours can originate from dental follicles, we hypothesized that the BRAF and KRAS mutations might be early events in odontogenic tumours tumourigenesis. We aimed to assess BRAF and KRAS mutations in dental follicles associated with asymptomatic impacted teeth. DESIGN: Forty-eight dental follicles containing odontogenic epithelial remnants were included in the study. As ameloblastomas most often occur in the posterior mandible and adenomatoid odontogenic tumours have a predilection for the anterior jaws, we assessed by allele-specific qPCR the presence of BRAF p.V600E in 32 dental follicles associated with impacted 3rd mandibular molar teeth and KRAS p.G12 V and KRAS p.G12R mutations in 16 dental follicle specimens obtained from around impacted anterior teeth. Sanger sequencing was used as an additional method. RESULTS: None of the dental follicle cases tested positive for the mutations. CONCLUSION: In conclusion, we tried to detect the early genetic events associated with odontogenic tumours development in dental follicles, but we were unable to showcase that BRAF p.V600E and KRAS p.G12R or p.G12 V mutations are the early genetic events associated with odontogenic tumours development.