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Gene | BRAF |
Variant | K601E |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | BRAF K601E lies within the activation segment in the kinase domain of the Braf protein (PMID: 15343278). K601E results in increased Braf kinase activity and downstream activation of MEK and ERK in cell culture (PMID: 22798288, PMID: 28783719, PMID: 32059434), and induces cell proliferation and cell viability in culture (PMID: 29533785, PMID: 18697864). |
Associated Drug Resistance | |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF K601E BRAF mutant BRAF K601X BRAF K601E |
Transcript | NM_004333.6 |
gDNA | chr7:g.140753334T>C |
cDNA | c.1801A>G |
Protein | p.K601E |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004333 | chr7:g.140753334T>C | c.1801A>G | p.K601E | RefSeq | GRCh38/hg38 |
NM_001354609.1 | chr7:g.140753334T>C | c.1801A>G | p.K601E | RefSeq | GRCh38/hg38 |
NM_004333.5 | chr7:g.140753334T>C | c.1801A>G | p.K601E | RefSeq | GRCh38/hg38 |
NM_004333.6 | chr7:g.140753334T>C | c.1801A>G | p.K601E | RefSeq | GRCh38/hg38 |
XM_005250045 | chr7:g.140753334T>C | c.1801A>G | p.K601E | RefSeq | GRCh38/hg38 |
NM_001378474.1 | chr7:g.140753334T>C | c.1801A>G | p.K601E | RefSeq | GRCh38/hg38 |
NM_001378468.1 | chr7:g.140753334T>C | c.1801A>G | p.K601E | RefSeq | GRCh38/hg38 |
NM_001354609.2 | chr7:g.140753334T>C | c.1801A>G | p.K601E | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF S363F BRAF K601E | melanoma | sensitive | Encorafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
BRAF S363F BRAF K601E | melanoma | sensitive | Encorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Braftovi (encorafenib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
BRAF S363F BRAF K601E | melanoma | sensitive | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Tafinlar (dabrafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
BRAF S363F BRAF K601E | melanoma | sensitive | Trametinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
BRAF S363F BRAF K601E | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
BRAF S363F BRAF K601E | melanoma | sensitive | Cobimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Cotellic (cobimetinib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
BRAF S363F BRAF K601E | melanoma | sensitive | Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mektovi (binimetinib) inhibited growth of a melanoma cell line harboring BRAF K601E, as well as BRAF S363F, in culture (PMID: 29903896). | 29903896 |
BRAF K601E MAP2K1 V211D | colon cancer | predicted - resistant | Binimetinib + Panitumumab | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic colon cancer harboring BRAF K601E developed progressive disease after 6 weeks of Mektovi (binimetinib) and Vectibix (panitumumab) combination treatment, MAP2K1 V211D was identified as a co-occuring mutation in the biopsy from the new metastasis site (PMID: 31227518). | 31227518 |
BRAF K601E MAP2K1 V211D | colon cancer | sensitive | MAP855 | Preclinical - Pdx | Actionable | In a preclinical study, MAP855 inhibited Rsk and Erk phosphorylation, and resulted in 30% tumor regression in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). | 31227518 |
BRAF K601E MAP2K1 V211D | colon cancer | resistant | Binimetinib | Preclinical - Pdx | Actionable | In a preclinical study, Mektovi (binimetinib) did not inhibit Rsk and Erk phosphorylation, and had no effect on tumor growth in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). | 31227518 |
BRAF K601E MAP2K1 V211D | colon cancer | resistant | Binimetinib + Cetuximab | Preclinical - Pdx | Actionable | In a preclinical study, Mektovi (binimetinib) and Erbitux (cetuximab) combination did not inhibit Rsk and Erk phosphorylation, and had no effect on tumor growth in patient-derived xenograft (PDX) models of metastatic colon cancer harboring BRAF K601E and MAP2K1 V211D (PMID: 31227518). | 31227518 |