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Gene | BRAF |
Variant | del exon4-8 |
Impact List | deletion |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | BRAF del exon4-8 indicates the deletion of exons 4-8 of the BRAF gene (PMID: 33216826). Del exon4-8 has been associated with resistance to MEK inhibitors (PMID: 33216826) and RAF inhibitors (PMID: 22113612) in culture, and is predicted to lead to a gain of Braf protein function due to the deletion of the CR1 autoinhibitory domain and preservation of the protein kinase domain (PMID: 23890088, PMID: 22113612). |
Associated Drug Resistance | Y |
Category Variants Paths |
BRAF mutant BRAF act mut BRAF del exon4-8 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
BRAF del exon4-8 BRAF V600E | melanoma | predicted - resistant | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, a BRAF exon 4-8 deletion variant (reported as p61) was identified in the post-progression plasma ctDNA of two patients with metastatic melanoma harboring BRAF V600E who previously responded to treatment with the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) (PMID: 33216826). | 33216826 |
BRAF del exon4-8 BRAF V600E | melanoma | sensitive | Binimetinib + PF-07799933 | Preclinical - Pdx | Actionable | In a preclinical study, treatment with the combination of PF-07799933 and Mektovi (binimetinib) resulted in tumor regression in a patient-derived xenograft (PDX) model of melanoma harboring BRAF V600E and a BRAF exon 4-8 deletion variant (reported as p61 splice variant) (PMID: 38691346). | 38691346 |
BRAF del exon4-8 BRAF V600E | melanoma | predicted - resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a clinical case study, a deletion of BRAF exons 4-8 was identified in the post-progression biopsy of a melanoma patient harboring BRAF V600E who was treated with Zelboraf (vemurafenib) (PMID: 22113612). | 22113612 |