ArticleBMC cancer2019
Clinical mutational profiling and categorization of BRAF mutations in melanomas using next generation sequencing.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 68 citations in OpenAlex.
- Precision oncology in advanced melanoma: molecular landscapes and personalized therapy recommendations from the Molecular Tumor Board Freiburg.NPJ precision oncology · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Oncogenic Signalling Pathways in Cancer Immunotherapy: Leader or Follower in This Delicate Dance?International journal of molecular sciences · 2025Review
- Real-world genomic landscape of colon and rectal cancer.FEBS open bio · 2025Article
- Design, Virtual Screening, Molecular Docking, ADME and Cytotoxicity Studies of 1,3,5-Triazine Containing Heterocyclic Scaffolds as Selective BRAF Monomeric, Homo and Heterodimeric Inhibitors.Combinatorial chemistry & high throughput screening · 2025Article
- Inhibition and degradation of NRAS with a pan-NRAS monobody.Oncogene · 2024Article
- Therapeutic vulnerabilities and pan-cancer landscape of BRAF class III mutations in epithelial solid tumors.BJC reports · 2024Article
- Melanoma genomics - will we go beyond BRAF in clinics?Journal of cancer research and clinical oncology · 2024Review
- BRAFNPJ precision oncology · 2024Review
- Article
- The evolution of BRAF-targeted therapies in melanoma: overcoming hurdles and unleashing novel strategies.Frontiers in oncology · 2024Review
- PredictingJournal of skin cancer · 2024Article
- BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers.Cancers · 2023Review
- Oncogenic alterations reveal key strategies for precision oncology in melanoma treatment.Annals of translational medicine · 2022Article
- New Directions in the Therapy of Glioblastoma.Cancers · 2022Review
- Structure-based prediction of BRAF mutation classes using machine-learning approaches.Scientific reports · 2022Article
- Genomic Landscape, Clinical Features and Outcomes of Non-Small Cell Lung Cancer Patients HarboringCancers · 2022Article
- Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma.Journal of clinical medicine · 2022Review
- Article
- Concurrent RAS and RAS/BRAF V600E Variants in Colorectal Cancer: More Frequent Than Expected? A Case Report.Frontiers in oncology · 2022Article
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundAnalysis of melanomas for actionable mutations has become the standard of care. Recently, a classification scheme has been proposed that categorizes BRAF mutations based on their mechanisms for activation of the MAPK pathway.
methodsIn this analysis BRAF, KIT, NRAS, and PIK3CA mutations were examined by next generation sequencing (NGS) in 446 melanomas in a clinical diagnostic setting. KRAS and HRAS were also analyzed to elucidate coexisting BRAF and RAS mutations. BRAF mutations were categorized into class-1 (kinase-activated, codon 600), class-2 (kinase-activated, non-codon 600) and class-3 (kinase-impaired), based on the newly proposed classification scheme.
resultsNGS demonstrated high analytic sensitivity. Among 355 mutations detected, variant allele frequencies were 2-5% in 21 (5.9%) mutations and 2-10% in 47 (13%) mutations. Mutations were detected in BRAF (42%), NRAS (25%), KIT (4.9%) and PIK3CA (2.7%). The incidence of class-1, class-2 and class-3 mutations were 33% (26% p.V600E and 6.1% p.V600K), 3.1 and 4.9% respectively. With a broader reportable range of NGS, class-1, class-2 and class-3 mutations accounted for 77, 7.4 and 12% of all BRAF mutations. Class-3 mutations, commonly affecting codons 594, 466 and 467, showed a higher incidence of coexisting RAS mutations, consistent with their RAS-dependent signaling. Significant association with old age and primary tumors of head/neck/upper back suggest chronic solar damage as a contributing factor for melanomas harboring BRAF p.V600K or class-3 mutations.
conclusionThis study categorizes the range, frequency, coexisting driver mutations and clinical characteristics of the three classes of BRAF mutations in a large cohort of melanomas in a clinical diagnostic setting. Further prospective studies are warranted to elucidate the clinical outcomes and benefits of newly developed targeted therapy in melanoma patients carrying each class of BRAF mutation.
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