ArticleOncotarget2017
Heterogeneity and frequency of BRAF mutations in primary melanoma: Comparison between molecular methods and immunohistochemistry.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Genetic Concordance in Primary Cutaneous Melanoma and Matched Metastasis: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2023Pooled it
- Widespread atypical UV-induced mutations form in single-stranded DNA.Science advances · 2026Article
- Association BetweenDiseases (Basel, Switzerland) · 2026Article
- Epidemiology and Treatment Patterns of Stage III Resectable Melanoma Treated with Adjuvant Therapy: A Real-World Study Using the SNDS Database in France.Dermatology and therapy · 2026Article
- Comparative Dermoscopic Analysis of Melanoma In Situ Versus Thin Invasive Melanoma Considering BRAF Mutational Status.Journal of clinical medicine · 2025Article
- Mechanisms of Melanoma Progression and Treatment Resistance: Role of Cancer Stem-like Cells.Cancers · 2024Review
- Ataxia-Telangiectasia Mutated Loss of Heterozygosity in Melanoma.International journal of molecular sciences · 2022Article
- Identification of Dihydrolipoamide Dehydrogenase as Potential Target of Vemurafenib-Resistant Melanoma Cells.Molecules (Basel, Switzerland) · 2022Article
- Computer-Assisted Annotation of Digital H&E/SOX10 Dual Stains Generates High-Performing Convolutional Neural Network for Calculating Tumor Burden in H&E-Stained Cutaneous Melanoma.International journal of environmental research and public health · 2022Article
- The Role and Potential ofDiagnostics (Basel, Switzerland) · 2022Review
- Characterization and Clinical Utility ofCancers · 2021Article
- BRAF Heterogeneity in Melanoma.Current treatment options in oncology · 2021Review
- Quality assessment of a clinical next-generation sequencing melanoma panel within the Italian Melanoma Intergroup (IMI).Diagnostic pathology · 2020Article
- Comparison ofJournal of clinical medicine · 2020Article
- Detection of Gene Mutations in Liquid Biopsy of Melanoma Patients: Overview and Future Perspectives.Current treatment options in oncology · 2020Review
- Article
- The Current State of Molecular Testing in the BRAF-Mutated Melanoma Landscape.Frontiers in molecular biosciences · 2020Review
- Response to Ipilimumab/Nivolumab Rechallenge and BRAF Inhibitor/MEK Inhibitor Rechallenge in a Patient with Advanced Metastatic Melanoma Previously Treated with BRAF Targeted Therapy and Immunotherapy.Case reports in oncological medicine · 2020Article
- Dynamic and unpredictable changes in mutant allele fractions of BRAF and NRAS during visceral progression of cutaneous malignant melanoma.BMC cancer · 2019Article
- Combining molecular and immunohistochemical analyses of key drivers in primary melanomas: interplay between germline and somatic variations.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Finding the best technique to identify BRAF mutations with a high sensitivity and specificity is mandatory for accurate patient selection for target therapy. BRAF mutation frequency ranges from 40 to 60% depending on melanoma clinical characteristics and detection technique used.Intertumoral heterogeneity could lead to misinterpretation of BRAF mutational status; this is especially important if testing is performed on primary specimens, when metastatic lesions are unavailable.Aim of this study was to identify the best combination of methods for detecting BRAF mutations (among peptide nucleic acid - PNA-clamping real-time PCR, immunohistochemistry and capillary sequencing) and investigate BRAF mutation heterogeneity in a series of 100 primary melanomas and a subset of 25 matched metastatic samples.Overall, we obtained a BRAF mutation frequency of 62%, based on the combination of at least two techniques. Concordance between mutation status in primary and metastatic tumor was good but not complete (67%), when agreement of at least two techniques were considered. Next generation sequencing was used to quantify the threshold of detected mutant alleles in discordant samples. Combining different methods excludes that the observed heterogeneity is technique-based. We propose an algorithm for BRAF mutation testing based on agreement between immunohistochemistry and PNA; a third molecular method could be added in case of discordance of the results. Testing the primary tumor when the metastatic sample is unavailable is a good option if at least two methods of detection are used, however the presence of intertumoral heterogeneity or the occurrence of additional primaries should be carefully considered.
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