RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
[Paper-level Aggregated] PMCID: PMC3266695
Evidence Type(s): Functional
Summary: Mutation: V600E | Summary: The BRAF(V600E) mutation alters the molecular function of the BRAF protein, affecting its dimerization and signaling activity in the context of RAS activation.
Gene→Variant (gene-first): BRAF(673):V600E
Genes: BRAF(673)
Variants: V600E
RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
[Paper-level Aggregated] PMCID: PMC3266695
Evidence Type(s): Oncogenic
Summary: Mutation: V600E | Summary: The BRAF(V600E) mutation contributes to tumor development and progression in melanoma, demonstrating its oncogenic potential.
Gene→Variant (gene-first): BRAF(673):V600E
Genes: BRAF(673)
Variants: V600E
RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
[Paper-level Aggregated] PMCID: PMC3266695
Evidence Type(s): Predictive
Summary: Mutation: V600E | Summary: The BRAF(V600E) mutation is associated with sensitivity to RAF inhibitors in melanoma, indicating its predictive value for therapeutic response.
Gene→Variant (gene-first): BRAF(673):V600E
Genes: BRAF(673)
Variants: V600E
Activated RAS promotes dimerization of members of the RAF kinase family. ATP-competitive RAF inhibitors activate ERK signaling by transactivating RAF dimers. In melanomas with mutant BRAF(V600E), levels of RAS activation
[Paragraph-level] PMCID: PMC3266695 Section: ABSTRACT PassageIndex: 2
Evidence Type(s): Predictive, Oncogenic, Functional
Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF(V600E) mutation is associated with sensitivity to RAF inhibitors in melanoma, indicating its predictive value for therapeutic response. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF(V600E) mutation contributes to tumor development and progression in melanoma, demonstrating its oncogenic potential. Evidence Type: Functional | Mutation: V600E | Summary: The BRAF(V600E) mutation alters the molecular function of the BRAF protein, affecting its dimerization and signaling activity in the context of RAS activation.
Gene→Variant (gene-first): 673:V600E
Genes: 673
Variants: V600E
RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
[Paper-level Aggregated] PMCID: PMC3266695
Evidence Type(s): Oncogenic, Predictive, Functional
Justification: Oncogenic: The text discusses the presence of the BRAF(V600E) mutation in melanomas and its role in promoting tumor growth, indicating its oncogenic potential. Predictive: The evidence suggests that the presence of BRAF(V600E) is predictive of response to RAF inhibitors, as these drugs have remarkable clinical activity in patients with this specific mutation. Functional: The text describes the functional consequences of the BRAF(V600E) mutation, including its role in dimerization and resistance to RAF inhibitors, demonstrating its functional impact on ERK signaling.
Gene→Variant (gene-first): BRAF(673):V600E
Genes: BRAF(673)
Variants: V600E
Activated RAS promotes dimerization of members of the RAF kinase family. ATP-competitive RAF inhibitors activate ERK signaling by transactivating RAF dimers. In melanomas with mutant BRAF(V600E), levels of RAS activation
[Paragraph-level] PMCID: PMC3266695 Section: ABSTRACT PassageIndex: 2
Evidence Type(s): Predictive, Oncogenic
Justification: Predictive: The passage discusses how the presence of the BRAF(V600E) variant correlates with the clinical activity of RAF inhibitors in melanoma patients, indicating a relationship between the variant and treatment response. Oncogenic: The BRAF(V600E) variant is described as contributing to tumor development and progression, particularly in the context of its role in ERK signaling and the development of resistance mechanisms in melanoma.
Gene→Variant (gene-first): 673:V600E
Genes: 673
Variants: V600E