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

Ameloblastoma (AM) is a benign, although aggressive, epithelial odontogenic tumour originating from tooth‐forming tissues or remnants. Its aetiopathogenesis remains unclear; however, molecular analysis techniques have allowed researchers to progress in understanding its genetic basis. The high frequency of BRAF p.V600E as a main driver mutation in AM is well established; nevertheless, it is insufficient to explain its tumourigenesis. In this review, we aimed to integrate the current knowledge about the biology of AM and to describe the main genetic alterations reported, focusing on the findings of large‐scale sequencing and gene expression profiling techniques. Current evidence shows that besides BRAF mutation and activation of the MAPK pathway, alterations in Hedgehog and Wnt/β‐catenin pathway‐related genes are also involved in AM pathogenesis. Recently, a tumour suppressor gene, KMT2D, has been reported as mutated by different research groups. The biological impact of these mutations in the pathogenesis of AM has yet to be elucidated. Further studies are needed to clarify the impact of these findings in the identification of novel biomarkers that could be useful for diagnosing, classifying, and molecular targeting this neoplasm.

Section: Discussionmentioning

confidence: 98%

Molecular pathogenesis of ameloblastoma

Marín‐Márquez,

Kirby,

Hunter

2024

“…Several recent systematic reviews have conducted meta‐analyses regarding the correlation between BRAF and AM recurrence 29,30 . However, these reviews have not thoroughly evaluated the clinical characteristics and diagnostic efficacy associated with BRAF mutations.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological characteristics and diagnostic accuracy of BRAF mutations in ameloblastoma: A Bayesian network analysis

Zhang,

Liu

et al. 2024

ObjectiveThis Bayesian network meta‐analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy.Materials and MethodsFour electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation.ResultsA total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2–4.5), mandible site (OR, 3.6; 95% CrI: 2.7–5.2), and unicystic (OR, 1.6; 95% CrI: 1.1–2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups.ConclusionsThe incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.

“…2 Over 65% of the ameloblastomas harbor a missense activating mutation in RAF proto-oncogene, known as BRAF V600E. 1,3,4 This mutation is responsible for the codification of an altered protein that disrupts cell signaling in MAPK pathway and ultimately leads to neoplastic transformation. 2,5,6 Patients with ameloblastoma that displays BRAF mutations are potentially eligible for targeted therapy using MAPK pathway (BRAF, MEK, ERK) inhibitors.…”

Section: Introductionmentioning

confidence: 99%

It was not possible to detect BRAF V600E mutation in circulating cell‐free DNA from patients with ameloblastoma: A diagnostic accuracy study

Martins‐de‐Barros,

da Costa Araújo,

Barros

et al. 2024

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BackgroundThe objective of this study is to evaluate the diagnostic accuracy of plasma‐based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell‐free DNA from patients with ameloblastoma.MethodsThis is a prospective diagnostic accuracy study conducted based on the Standards for Reporting Diagnostic Accuracy recommendations. The index test was the plasma‐based liquid biopsy, whereas the reference standard was the conventional tissue biopsy. The target condition was the detection of BRAF V600E mutation. The study population consisted of individuals with ameloblastoma recruited from three tertiary hospitals from Brazil. A negative control group composed of three individuals with confirmed wild‐type BRAF lesions were included. The participants underwent plasma circulating cell‐free DNA and tumor tissue DNA isolation, and both were submitted to using competitive allele‐specific TaqMan™ real‐time polymerase chain reaction technology mutation detection assays. Sensitivity and specificity measures and positive and negative predictive values were calculated.ResultsTwelve patients with conventional ameloblastoma were included. BRAF V600E mutation was detected in 11/12 (91.66%) ameloblastoma tissue samples. However, the mutation was not detected in any of the plasma‐based liquid biopsy circulating cell‐free DNA samples in both ameloblastomas and negative control group. The sensitivity and specificity of plasma‐based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell‐free DNA was 0.0 and 1.0, respectively. The agreement between index test and reference standard results was 26.66%.ConclusionPlasma‐based liquid biopsy does not seem to be an accurate method for the detection of the BRAF V600E mutation in circulating circulating cell‐free DNA from patients with ameloblastoma, regardless of tumor size, anatomic location, recurrence status, and other clinicopathological features.