Genetic study of the BRAF gene reveals new variants and high frequency of the V600E mutation among Iranian ameloblastoma patients

Abstract

Background Ameloblastoma is a benign, slow‐growing and locally invasive tumor. It is one of the most prevalent odontogenic tumors, with an incidence rate of 1% of all oral tumors and approximately 18% of odontogenic tumors. A group of genes have been investigated in patients with ameloblastoma. The BRAF V600E mutation has been implicated as the most common mutation in ameloblastoma. The presence or absence of this mutation has been associated with several clinicopathological properties, including location, age at diagnosis, histology, and prognosis. Although some populations have been investigated so far, little data are available on the Iranian population. The current research was launched to study the BRAF V600E mutation among a cohort of Iranian patients with ameloblastoma. Methods In this clinicopathological and molecular biology study, a total of 19 formalin‐fixed, paraffin‐embedded tissues were studied. DNA extraction was performed, followed by PCR‐sequencing of exons 10 and 15 of the BRAF gene to identify mutations. In silico analysis was performed for the identified variants. Results were analyzed by T test, Chi‐square, and Fisher's exact test. Results Totally, 12 of 19 samples (63%) harbored the p. V600E hotspot mutation. In addition, we identified several variants, two of which were novel. The c.1769T>G (p. V590G) and c.1751C>T (p.L584F) as the novel variants showed a possible damaging effect by in silico analysis. No variant was found within exon 10. Conclusions Our study confirms the role of BRAF mutations in ameloblastoma in the Iranian patients studied.

High prevalence of BRAF V600E mutations in Korean patients with ameloblastoma: Clinicopathological significance and correlation with epithelial‐mesenchymal transition

“…As summarized in Table , associations of BRAF V600E mutations in ameloblastoma with clinicopathological factors have been analyzed in previous works . Consistent with previous findings, BRAF V600E mutation status was not associated with sex or histologic patterns in this study. In contrast, discordant results have been reported with regard to other clinicopathological factors in previous and current studies.…”

“…The BRAF V600E mutation was identified in 27 of the 30 ameloblastoma patients by Sanger sequencing (Table ), and other variants, except for p.V600E (c.1799T>A), were not detected in exon 15 of the BRAF gene (Figure A and B). The prevalence of BRAF V600E mutations observed in this study (90.0%) was higher than any other BRAF V600E mutation rate previously reported in patients with ameloblastoma (range, 42.9%‐82.4%; mean, 62.4%; Table ) . Of 27 immunohistochemically stained sections, 17 cases were positive for BRAF V600E (Figure C) and 10 cases showed negative staining including seven false‐negative cases (Figure D).…”

“…The presence and prevalence of BRAF V600E mutations in ameloblastoma have been investigated in patients from Europe, the United States, South America, and the Middle East . Reported prevalence rates ranged from 42.9% to 82.4%, and collectively, 98 of 157 patients (62.4%) harbored the BRAF V600E mutation (Table ).…”

“…Among these mutations, BRAF V600E, which is caused by a missense mutation T1799A, is most commonly found in human tumors, especially papillary thyroid carcinoma (PTC), melanoma, and colorectal cancer . Over the past few years, BRAF V600E mutations have also been detected at a high frequency in ameloblastoma, the most common and clinically significant epithelial odontogenic tumor, but their prevalence has not yet been reported in East Asian patients with ameloblastoma. The BRAF V600E mutation is a potential therapeutic target, and thus, several BRAF inhibitors have been developed for cancer treatment …”

Advancements in MAPK signaling pathways and MAPK‐targeted therapies for ameloblastoma: A review

“…[17][18][19] Maryam reported a BRAF mutation rate of 63.2% among Iranian AM patients, and the mutation rate was not significantly influenced by tumor distribution, type, mean age, and the genomic location of the mutation. 20 without BRAF V600E mutations were associated with an increased rate of local recurrence. 22 A brief overview of the positive IHC results of BRAF-V600E in AM is presented in Table 2, and the results suggested that VE1 IHC performed on undecalcified tissue sections may be a valid surrogate for BRAF V600E genetic testing.…”