An immunohistochemical and genetic study of BRAFV600E mutation in Japanese patients with ameloblastoma

Seki‐Soda, Mai; Sano, Takaaki; Ito, Kenta; Yokoo, Satoshi; Oyama, Tetsunari

doi:10.1111/pin.12899

Cited by 23 publications

(38 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

See 1 more Smart Citation

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

Guimarães

Coura

Gomez

et al. 2021

Front. Oral. Health

View full text Add to dashboard Cite

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.

show abstract

Section: Ameloblastomamentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…A BRAF mutation, causing valine to glutamic acid substitution at codon 600 (V600E), is present in 40-60% of ameloblastoma cases with mutation-dependent mitogen-activated protein kinase (MAPK) pathway activation [6][7][8][9]. Several studies have described cases of patients with a BRAFV600E mutant that were successfully treated with BRAF inhibitors [10][11][12], suggesting that BRAFV600E signalling might be involved in the development of ameloblastoma.…”

Section: Introductionmentioning

confidence: 99%

RAF1–MEK/ERK pathway‐dependent ARL4C expression promotes ameloblastoma cell proliferation and osteoclast formation

Fujii

Ishibashi

Kokura

et al. 2021

The Journal of Pathology

View full text Add to dashboard Cite

Ameloblastoma is an odontogenic neoplasm characterized by slow intraosseous growth with progressive jaw resorption. Recent reports have revealed that ameloblastoma harbours an oncogenic BRAFV600E mutation with mitogenactivated protein kinase (MAPK) pathway activation and described cases of ameloblastoma harbouring a BRAFV600E mutation in which patients were successfully treated with a BRAF inhibitor. Therefore, the MAPK pathway may be involved in the development of ameloblastoma; however, the precise mechanism by which it induces ameloblastoma is unclear. The expression of ADP-ribosylation factor (ARF)-like 4c (ARL4C), induced by a combination of the EGF-MAPK pathway and Wnt/β-catenin signalling, has been shown to induce epithelial morphogenesis. It was also reported that the overexpression of ARL4C, due to alterations in the EGF/RAS-MAPK pathway and Wnt/β-catenin signalling, promotes tumourigenesis. However, the roles of ARL4C in ameloblastoma are unknown. We investigated the involvement of ARL4C in the development of ameloblastoma. In immunohistochemical analyses of tissue specimens obtained from 38 ameloblastoma patients, ARL4C was hardly detected in non-tumour regions but tumours frequently showed strong expression of ARL4C, along with the expression of both BRAFV600E and RAF1 (also known as C-RAF). Loss-of-function experiments using inhibitors or siRNAs revealed that ARL4C elevation depended on the RAF1-MEK/ERK pathway in ameloblastoma cells. It was also shown that the RAF1-ARL4C and BRAFV600E-MEK/ ERK pathways promoted cell proliferation independently. ARL4C-depleted tumour cells (generated by knockdown or knockout) exhibited decreased proliferation and migration capabilities. Finally, when ameloblastoma cells were co-cultured with mouse bone marrow cells and primary osteoblasts, ameloblastoma cells induced osteoclast formation. ARL4C elevation in ameloblastoma further promoted its formation capabilities through the increased RANKL expression of mouse bone marrow cells and/or primary osteoblasts. These results suggest that the RAF1-MEK/ ERK-ARL4C axis, which may function in cooperation with the BRAFV600E-MEK/ERK pathway, promotes ameloblastoma development.

show abstract

“…3,4 Ensuing studies in a variety of patient populations have further expanded on the frequency and variation of this mutation in ameloblastoma cell lines and tumor specimens. [5][6][7][8][9] Fregnani et al 10 found that BRAF V600E mutation correlates with more aggressive behavior as measured by recurrence, multilocular radiographic appearance, and disruption of basal bone. Investigations by Brown et al 3 and Kelppe et al 7 found the mutation to be associated with earlier age of occurrence, though studies by other groups found no such association.…”

Section: Introductionmentioning

confidence: 99%

“…Investigations by Brown et al 3 and Kelppe et al 7 found the mutation to be associated with earlier age of occurrence, though studies by other groups found no such association. 5,6,8,11 Multiple reports have noted that the BRAF V600E mutation appears almost exclusively in mandibular lesions. 3,4,11 BRAF V600E mutation is well documented in a variety of neoplasms including melanoma, papillary thyroid cancer and colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

Treatment of a BRAF V600E Positive Ameloblastoma in a Pediatric Patient with MEK Inhibitor Monotherapy

Daws

Chaiyasate

Lehal

2021

FACE

View full text Add to dashboard Cite

Ameloblastomas are uncommon tumors of the odontogenic epithelium standardly treated with radical resection. Recent studies of the genetic landscape of ameloblastoma have revealed the frequent presence of the BRAF V600E mutation, suggesting a possible role for targeted chemotherapy. We present the case of a primary mandibular ameloblastoma found in a 13-year-old female with confirmed BRAF V600E mutation. Prior to invasive surgical intervention she was treated for 8 weeks with the MEK inhibitor trametinib, but her tumor demonstrated little radiographic, clinical, or histologic response. Previous case reports have shown ameloblastoma in adult patients to be responsive to other agents targeting the MAPK pathway. Our observations in the presented case demonstrate the need for further research into the utility of targeted chemotherapy in ameloblastoma treatment.

show abstract

An immunohistochemical and genetic study of BRAF^V600E mutation in Japanese patients with ameloblastoma

Cited by 23 publications

References 23 publications

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

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

RAF1–MEK/ERK pathway‐dependent ARL4C expression promotes ameloblastoma cell proliferation and osteoclast formation

Treatment of a BRAF V600E Positive Ameloblastoma in a Pediatric Patient with MEK Inhibitor Monotherapy

Contact Info

Product

Resources

About