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  2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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    1. karim2001khoury 19 Feb 2026
      COT/MAP3K8 drives resistance to RAF inhibition through MAP kinase pathway reactivation

      [Paper-level Aggregated] PMCID: PMC3058384

      Evidence Type(s): Oncogenic, Predictive, Functional

      Justification: Oncogenic: The B-RAFV600E mutation is described as an oncogenic mutation found in a significant percentage of malignant melanomas, indicating its role in cancer development. Predictive: The B-RAFV600E mutation predicts a dependency on the MAPK signaling cascade in melanoma, which is supported by the success of RAF and MEK inhibitors in clinical trials. Functional: The study functionally interrogates resistance mechanisms to a selective RAF kinase inhibitor in B-RAFV600E cell lines, identifying MAP3K8 as a factor driving resistance, demonstrating the functional implications of the variant.

      Gene→Variant (gene-first): BRAF(673):B-RAFV600E BRAF(673):serine/threonine

      Genes: BRAF(673)

      Variants: B-RAFV600E serine/threonine

      CIViC paper-level aggregated PMC3058384
    2. karim2001khoury 19 Feb 2026
      Oncogenic mutations in the serine/threonine kinase B-RAF are found in 50-70% of malignant melanomas. Pre-clinical studies have demonstrated that the B-RAFV600E mutation predicts a dependency on the mitogen activated prot

      [Paragraph-level] PMCID: PMC3058384 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The B-RAFV600E mutation predicts a dependency on the MAPK signaling cascade in melanoma, and this is validated by the success of RAF and MEK inhibitors in clinical trials, indicating a correlation with treatment response. Oncogenic: The passage discusses oncogenic mutations in B-RAF, specifically the B-RAFV600E mutation, which is implicated in tumor development and progression in malignant melanomas.

      Gene→Variant (gene-first): 673:B-RAFV600E 673:serine/threonine

      Genes: 673

      Variants: B-RAFV600E serine/threonine

      CIViC paragraph-level PMC3058384 Predictive Oncogenic
    3. karim2001khoury 19 Feb 2026
      Oncogenic mutations in the serine/threonine kinase B-RAF are found in 50-70% of malignant melanomas. Pre-clinical studies have demonstrated that the B-RAFV600E mutation predicts a dependency on the mitogen activated prot

      [Paragraph-level] PMCID: PMC3058384 Section: ABSTRACT PassageIndex: 1

      Evidence Type(s): Predictive, Oncogenic

      Justification: Predictive: The B-RAFV600E mutation predicts a dependency on the MAPK signaling cascade in melanoma, and this is validated by the success of RAF and MEK inhibitors in clinical trials, indicating a correlation with treatment response. Oncogenic: The passage discusses oncogenic mutations in B-RAF, specifically the B-RAFV600E mutation, which is implicated in tumor development and progression in malignant melanomas.

      Gene→Variant (gene-first): 673:B-RAFV600E 673:serine/threonine

      Genes: 673

      Variants: B-RAFV600E serine/threonine

      CIViC paragraph-level PMC3058384 Predictive Oncogenic
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    pmc.ncbi.nlm.nih.gov/articles/PMC3058384/pdf/nihms248195.pdf