High frequency of BRAF V600E mutation in Iranian population ameloblastomas

Derakhshan, Samira; Aminishakib, Pouyan; Karimi, Abbas; Saffar, Hiva; Abdollahi, Amir; Mohammadpour, Hadiseh; Fard, M-J Kharazi; Memarha, A

doi:10.4317/medoral.23519

Cited by 17 publications

(22 citation statements)

References 26 publications

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“… 56 The disadvantages of each technique make the accuracy and the comparative analyses unreliable. Some authors reported an adequate agreement, 13 , 16 , 17 , 19 , 22 , 34 , 36 , 38 , 50 whereas others showed a high results variability between the detection methods. 15 , 20 , 26 , 29 , 37 , 41 , 49 Especially, a low sensitivity and a high specificity of immunohistochemistry have been demonstrated.…”

Section: Discussionmentioning

confidence: 97%

Identification of BRAF V600E mutation in odontogenic tumors by high-performance MALDI-TOF analysis

et al. 2022

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Odontogenic tumors are rare lesions with unknown etiopathogenesis. Most of them are benign, but local aggressiveness, infiltrative potential, and high recurrence rate characterize some entities. The MAP-kinase pathway activation can represent a primary critical event in odontogenic tumorigenesis. Especially, the BRAF V600E mutation has been involved in 80–90% of ameloblastic lesions, offering a biological rationale for developing new targeted therapies. The study aims to evaluate the BRAF V600E mutation in odontogenic lesions, comparing three different detection methods and focusing on the Sequenom MassARRAY System. 81 surgical samples of odontogenic lesions were subjected to immunohistochemical analysis, Sanger Sequencing, and Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometry (Sequenom). The BRAF V600E mutation was revealed only in ameloblastoma samples. Moreover, the presence of BRAF V600E was significantly associated with the mandibular site (ρ = 0.627; P value <0.001) and the unicystic histotype (ρ = 0.299, P value <0.001). However, any significant difference of 10-years disease-free survival time was not revealed. Finally, Sequenom showed to be a 100% sensitive and 98.1% specific, suggesting its high-performance diagnostic accuracy. These results suggest the MAP-kinase pathway could contribute to ameloblastic tumorigenesis. Moreover, they could indicate the anatomical specificity of the driving mutations of mandibular ameloblastomas, providing a biological rational for developing new targeted therapies. Finally, the high diagnostic accuracy of Sequenom was confirmed.

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Section: Discussionmentioning

confidence: 97%

Identification of BRAF V600E mutation in odontogenic tumors by high-performance MALDI-TOF analysis

et al. 2022

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“…In 2014, the pioneer study by the group of Heikinheimo reported for the first time recurrent activating BRAF p.V600E mutations in ameloblastomas [9]. Considering that MAPK/ERK signaling can be activated by stimulation of transmembrane receptors, including EGFR, and that overexpression of EGFR had previously been reported in ameloblastomas, when [9], [10], [51], [52], [53] e , [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [ V600E mutation in all five ameloblastic carcinoma samples evaluated and this frequency was much higher than reported by previous studies, and therefore we did not add the results to the other ones when calculating mutation frequency.…”

Section: Ameloblastomamentioning

confidence: 99%

“…They further reported the presence of BRAF p.V600E mutation in 67% (23/34) of ameloblastomas by using VE1 immunohistochemistry in cases not suitable for molecular evaluation [52]. Following these pieces of research, several studies have also assessed the presence of BRAF p.V600E in conventional ameloblastoma, either by molecular techniques or a combination of mutation screening and immunohistochemistry, with mutation frequencies varying from 55 to ∼90% [10,[53][54][55][56][57][58][59][60][61][62][63]. In two studies with limited sample numbers, the mutation was detected in all samples [2/2 [64] and 4/4 [65]].…”

Section: Ameloblastomamentioning

confidence: 99%

The Molecular Pathology of Odontogenic Tumors: Expanding the Spectrum of MAPK Pathway Driven Tumors

Guimarães

Coura

Gomez

et al. 2021

Front. Oral. Health

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Odontogenic tumors comprise a heterogeneous group of lesions that arise from the odontogenic apparatus and their remnants. Although the etiopathogenesis of most odontogenic tumors remains unclear, there have been some advances, recently, in the understanding of the genetic basis of specific odontogenic tumors. The mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK) pathway is intimately involved in the regulation of important cellular functions, and it is commonly deregulated in several human neoplasms. Molecular analysis performed by different techniques, including direct sequencing, next-generation sequencing, and allele-specific qPCR, have uncovered mutations in genes related to the oncogenic MAPK/ERK signaling pathway in odontogenic tumors. Genetic mutations in this pathway genes have been reported in epithelial and mixed odontogenic tumors, in addition to odontogenic carcinomas and sarcomas. Notably, B-Raf proto-oncogene serine/threonine kinase (BRAF) and KRAS proto-oncogene GTPase (KRAS) pathogenic mutations have been reported in a high proportion of ameloblastomas and adenomatoid odontogenic tumors, respectively. In line with the reports about other neoplasms that harbor a malignant counterpart, the frequency of BRAF p.V600E mutation is higher in ameloblastoma (64% in conventional, 81% in unicystic, and 63% in peripheral) than in ameloblastic carcinoma (35%). The objective of this study was to review MAPK/ERK genetic mutations in benign and malignant odontogenic tumors. Additionally, such genetic alterations were discussed in the context of tumorigenesis, clinical behavior, classification, and future perspectives regarding therapeutic approaches.

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“…[9][10][11] This mutation induces homeostatic activation of BRAF, which activates the RAF-MEK-ERK pathway and enhances the proliferative potential of tumor cells. The presence and prevalence of the BRAF V600E mutation in ameloblastoma have been reported in patients from various regions 6,7,[12][13][14][15][16][17][18] ; it ranges from 42.9% to 92.0%. In our study, the mutation was detected at a higher rate, that is, 83% of the patients.…”

Section: Discussionmentioning

confidence: 99%

“…This is in line with the false positive rate reported in the evaluation of BRAF mutations, using immunohistochemical staining with the VE1 antibody. 16,18,22 This could be attributed to sampling problems. Small tumor foci could be insufficient for PCR-based detection.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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High frequency of BRAF V600E mutation in Iranian population ameloblastomas

Cited by 17 publications

References 26 publications

Identification of BRAF V600E mutation in odontogenic tumors by high-performance MALDI-TOF analysis

Identification of BRAF V600E mutation in odontogenic tumors by high-performance MALDI-TOF analysis

The Molecular Pathology of Odontogenic Tumors: Expanding the Spectrum of MAPK Pathway Driven Tumors

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

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