ArticleApplied immunohistochemistry & molecular morphology : AIMM2015
BRAF and NRAS mutations are heterogeneous and not mutually exclusive in nodular melanoma.
Article in Applied immunohistochemistry & molecular morphology : AIMM, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- A Review of Melanoma Subtypes: Genetic and Treatment Considerations.Journal of surgical oncology · 2025Review
- Assessment of RAS-RAF-MAPK Pathway Mutation Status in Healthy Skin, Benign Nevi, and Cutaneous Melanomas: Pilot Study Using Droplet Digital PCR.International journal of molecular sciences · 2024Article
- Effects of BRAF V600E and NRAS mutational status on the progression-free survival and clinicopathological characteristics of patients with melanoma.Oncology letters · 2023Article
- Vemurafenib Drives Epithelial-to-Mesenchymal Transition Gene Expression in BRAF Inhibitor‒Resistant BRAFThe Journal of investigative dermatology · 2022Article
- Perspectives for Combining Viral Oncolysis With Additional Immunotherapies for the Treatment of Melanoma.Frontiers in molecular biosciences · 2022Review
- MUG Mel3 Cell Lines Reflect Heterogeneity in Melanoma and Represent a Robust Model for Melanoma in Pregnancy.International journal of molecular sciences · 2021Article
- Article
- Molecular Markers and Targets in Melanoma.Cells · 2021Review
- Unraveling the Wide Spectrum of Melanoma Biomarkers.Diagnostics (Basel, Switzerland) · 2021Review
- Emerging strategies to treat rare and intractable subtypes of melanoma.Pigment cell & melanoma research · 2021Review
- Molecular and Immune Biomarkers for Cutaneous Melanoma: Current Status and Future Prospects.Cancers · 2020Review
- Review
- A rare BRAF V600E mutation detected by next-generation sequencing in a superficial spreading melanoma: case report and potential diagnostic implications.Journal of the European Academy of Dermatology and Venereology : JEADV · 2020Article
- Targeted Therapy in Melanoma and Mechanisms of Resistance.International journal of molecular sciences · 2020Review
- Current Molecular Markers of Melanoma and Treatment Targets.International journal of molecular sciences · 2020Review
- Does the gene matter? Genotype-phenotype and genotype-outcome associations in congenital melanocytic naevi.The British journal of dermatology · 2020Article
- Primary squamous cell carcinoma of major salivary gland: "Sapienza Head and Neck Unit" clinical recommendations.Rare tumors · 2020Article
- Immunohistochemical and Molecular Features of Melanomas Exhibiting Intratumor and Intertumor Histomorphologic Heterogeneity.Cancers · 2019Article
- Clinical protein science in translational medicine targeting malignant melanoma.Cell biology and toxicology · 2019Article
- Challenging the heterogeneity of disease presentation in malignant melanoma-impact on patient treatment.Cell biology and toxicology · 2019Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibitors of RAF inhibit the MAPK pathway that plays an important role in the development and progression of those melanoma carrying the V600E BRAF mutation, but there's a subset of such patients who do not respond to the therapy. Various mechanisms of drug resistance have been proposed which include the clonal heterogeneity of the tumor. We have studied a population of nodular melanoma to investigate the intratumor and intertumor heterogeneity by Laser Capture Microdissection (LCM) analysis. Our results showed that BRAF and NRAS mutations were detected in 47% and 33% of nodular melanoma, respectively, and that there is a discrepancy in mutational pattern of tumoral sample because in the 36% of patients a different mutation, in at least 1 area of the tumor, was found by LCM analysis, giving evidence of the presence of different clonal cells populations. Moreover, we found that mutations in BRAF and NRAS are not mutually exclusive because they were simultaneously present in the same tumor specimens and we observed that when the 2 different mutations were present one is a high-frequency mutation and the other is a low-frequency mutation. This was more evident in lymphonodal metastasis that resulted from wild type to mutational analysis, but showed different mutations following LCM analysis. Therefore, we believed that, when primary tumoral sample results negative to mutational analysis, if it is possible, metastases should be investigated to verify the presence of mutations. Generally, it should be searched for other mutations, in addition to BRAF V600E, so as to better understand the mechanism of drug resistance.
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