Genetic Study of BRAF V600E and SMO L412F Mutations in Japanese Patients with Ameloblastoma

Abstract

Background and aim: Ameloblastoma is a benign, intraosseous, progressively growing, epithelial, odontogenic neoplasm. BRAF and SMO mutations have been reported in ameloblastoma. In this study, we evaluated BRAF V600E and SMO L412F mutations; and assessed the relationship between BRAF V600E mutant expression and the clinicopathological features in Japanese patients with ameloblastoma. Methods: We examined 24 formalin-fixed paraffin-embedded samples. All specimens were from patients with mandibular ameloblastoma: 20 were conventional ameloblastoma and 4 were unicystic ameloblastoma. The BRAF V600E mutation was assessed by Sanger sequencing and immunohistochemistry, and the SMO L412F mutation was assessed only by Sanger sequencing. Results: Twenty of the 24 (83%) ameloblastoma samples carried the BRAF V600E mutation; 22 of the 24 (92%) samples were immunohistochemically positive for BRAF V600E. However, the SMO L412F mutation was not detected in any of them. The BRAF V600E mutation status did not correlate with the clinicopathological features, such as age, sex, location, method, recurrence, and subtype. Conclusion: BRAF inhibitors could be a potential treatment option for Japanese patients with ameloblastoma, harboring the BRAF V600E mutation.

Differential expression of PEA3 in odontogenic cysts and tumors

“…Our results found a high expression of PEA3 in almost half of conventional AM samples (49.2%). According to numerous previous studies, BRAF V600E was detected in conventional AMs with varying levels of frequency (33.3%–92%) 22,25–27 . These further underpin the role of MAPK and its downstream target PEA3 in ameloblastoma pathogenesis.…”

“…According to numerous previous studies, BRAF V600E was detected in conventional AMs with varying levels of frequency (33.3%-92%). 22,[25][26][27] These further underpin the role of MAPK and its downstream target PEA3 in ameloblastoma pathogenesis. However, as a complex molecular cascade, upregulation of MAPK pathway by BRAF V600E may not only activate PEA3 expression but could also result in a stimulation of other transcription factors.…”

Does BRAF V600E mutation affect recurrence rate of ameloblastomas? Systematic review and meta‐analysis

“…Duplicate references were removed and the remaining titles and abstracts analyzed. Forty‐six articles were selected for full‐text analysis, with 21 9,10,12,16–33 studies meeting the criteria to be included in this systematic review. The PRISMA flow diagram showing the complete article selection process is illustrated in Figure S1.…”

“…Due to the disturbing effects of BRAF activating mutations in the MAPK signaling pathway, 36 many studies hypothesized that ameloblastomas harboring BRAF V600E mutations would be more aggressive and would have higher recurrence rates than wild-type BRAF ameloblastomas. [8][9][10][11][12][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] However, the overall results were inconclusive and varied widely among the studies.…”

“…Duplicate references were removed and the remaining titles and abstracts analyzed. Forty-six articles were selected for full-text analysis, with 21 9,10,12,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]…”