ArticleJournal of carcinogenesis2004
Constitutive activation of the Ras-Raf signaling pathway in metastatic melanoma is associated with poor prognosis.
Article in Journal of carcinogenesis, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 283 citations in OpenAlex.
- The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis.PloS one · 2012Pooled it
- Nilotinib in KIT-driven advanced melanoma: Results from the phase II single-arm NICAM trial.Cell reports. Medicine · 2024Trial
- Trial
- Comprehensive Genomic Profiling of Acral Melanoma: Insights From the AACR Project GENIE Database.The American Journal of dermatopathology · 2026Article
- MCLRP: enhanced prediction of anticancer drug response through low-rank matrix completion and transcriptomic profiling.BMC biology · 2025Article
- The IFNγ-CIITA-MHC II axis modulates melanoma cell susceptibility to NK-cell-mediated cytotoxicity.Molecular oncology · 2025Article
- Ancestry and somatic profile predict acral melanoma origin and prognosis.medRxiv : the preprint server for health sciences · 2025Article
- Pathogenic mutation hotspots in protein kinase domain structure.Protein science : a publication of the Protein Society · 2023Article
- Connecting the dots: Melanoma cell of origin, tumor cell plasticity, trans-differentiation, and drug resistance.Pigment cell & melanoma research · 2023Review
- Skin cancer, including related pathways and therapy and the role of luteolin derivatives as potential therapeutics.Medicinal research reviews · 2022Review
- MALAT1 as master regulator of biomarkers predictive of pan-cancer multi-drug resistance in the context of recalcitrant NRAS signaling pathway identified using systems-oriented approach.Scientific reports · 2022Article
- BRAF Heterogeneity in Melanoma.Current treatment options in oncology · 2021Review
- Prolonged response to treatment based on cell-free DNA analysis and molecular profiling in three patients with metastatic cancer: a case series.Therapeutic advances in medical oncology · 2021Article
- EmergingGenes · 2020Review
- Concordance and Discordance Rates of V-Raf Murine Sarcoma Viral Oncogene Homolog B1 (JMA journal · 2020Article
- Paired genetic analysis by next-generation sequencing of lung cancer and associated idiopathic pulmonary fibrosis.Cancer science · 2020Article
- Frequency and Clinicopathological Profile Associated with Braf Mutations in Patients with Advanced Melanoma in Spain.Translational oncology · 2020Article
- Synthesis and Evaluation of Artemisinin-Based Hybrid and Dimer Derivatives as Antimelanoma Agents.ACS omega · 2020Article
- Review
- Time-varying pattern of recurrence risk for localized melanoma in China.World journal of surgical oncology · 2020Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenes of the Raf family encode kinases that are regulated by Ras and mediate cellular responses to growth signals. Recently, it was shown that activating mutations of BRaf are found with high frequency in human melanomas. The Ras family member most often mutated in melanoma is NRas.
methodsThe constitutive activation of the Ras/Raf signaling pathway suggests an impact on the clinical course of the tumor. To address this notion, we analyzed tumor DNA from 114 primary cutaneous melanomas and of 86 metastatic lesions obtained from 174 patients for mutations in BRaf (exons 15 and 11) and NRas (exons 1 and 2) by direct sequencing of PCR products and correlated these results with the clinical course.
resultsIn 57.5% of the tumors either BRaf or NRas were mutated with a higher incidence in metastatic (66.3%) than in primary lesions (50.9%). Although the majority of BRaf mutations affected codon 599, almost 15% of mutations at this position were different from the well-described exchange from valine to glutamic acid. These mutations (V599R and V599K) also displayed increased kinase and transforming activity. Surprisingly, the additional BRaf variants D593V, G465R and G465E showed a complete loss of activity in the
conclusionWe demonstrate a high - albeit lower than initially anticipated - frequency of activating BRaf mutations in melanoma in the largest series of directly analyzed tumors reported to date. Notably, the clinical course of patients harboring activating BRaf mutations in metastatic melanoma was significantly affected by the presence of a constitutive BRaf activation in these.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.