COT/MAP3K8 drives resistance to RAF inhibition through MAP kinase pathway reactivation
[Paper-level Aggregated] PMCID: PMC3058384
Evidence Type(s): Oncogenic
Summary: Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation is associated with tumor development and progression in malignant melanomas, as it is found in 50-70% of these cases.
Gene→Variant (gene-first): BRAF(673):B-RAFV600E
Genes: BRAF(673)
Variants: B-RAFV600E
COT/MAP3K8 drives resistance to RAF inhibition through MAP kinase pathway reactivation
[Paper-level Aggregated] PMCID: PMC3058384
Evidence Type(s): Predictive
Summary: Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation predicts a dependency on the MAPK signaling cascade in melanoma, which has been validated by the success of RAF and MEK inhibitors in clinical trials.
Gene→Variant (gene-first): BRAF(673):B-RAFV600E
Genes: BRAF(673)
Variants: B-RAFV600E
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): Oncogenic, Predictive
Summary: Evidence Type: Oncogenic | Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation is associated with tumor development and progression in malignant melanomas, as it is found in 50-70% of these cases. Evidence Type: Predictive | Mutation: B-RAFV600E | Summary: The B-RAFV600E mutation predicts a dependency on the MAPK signaling cascade in melanoma, which has been validated by the success of RAF and MEK inhibitors in clinical trials.
Gene→Variant (gene-first): 673:B-RAFV600E 673:serine/threonine
Genes: 673
Variants: B-RAFV600E serine/threonine
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
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
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