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V600E is a mutation of the BRAF gene in which valine (V) is substituted by glutamic acid (E) at amino acid 600. [1] [2] It is a driver mutation in a proportion of certain diagnoses, including melanoma, [3] [4] hairy cell leukemia, [5] [6] papillary thyroid carcinoma, [7] [8] colorectal cancer, [9] non-small-cell lung cancer, [10] [11] Langerhans cell histiocytosis, [12] Erdheim–Chester ...
More than 30 mutations of the BRAF gene associated with human cancers have been identified. The frequency of BRAF mutations varies widely in human cancers, from more than 80% in melanomas and nevi , to as little as 0–18% in other tumors , such as 1–3% in lung cancers and 5% in colorectal cancer . [ 28 ]
In June 2018, the FDA approved the combination of a BRAF inhibitor encorafenib and a MEK inhibitor binimetinib for the treatment of un-resectable or metastatic melanoma with a BRAF V600E or V600K mutation. [186] Eventual resistance to BRAF and MEK inhibitors may be due to a cell surface protein known as EphA2 which is now being investigated. [187]
Vemurafenib only works in melanoma patients whose cancer has a V600E BRAF mutation (that is, at amino acid position number 600 on the B-Raf protein, the normal valine is replaced by glutamic acid). [4] About 60% of melanomas have this mutation. It also has efficacy against the rarer V600K BRAF (the normal valine is replaced by lysine) mutation ...
BRAF mutations are extremely rare in posterior uveal melanomas; [13] instead, uveal melanomas frequently harbor GNAQ/GNA11 mutations, a trait shared with blue nevi, nevus of Ota, and ocular melanosis. [14] [15] As seen in BRAF, mutations in GNAQ/GNA11 are early events in tumorigenesis and are not prognostic for tumor stage or later metastatic ...
Encorafenib is indicated in combination with binimetinib, for the treatment of people with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test; [2] in combination with cetuximab, for the treatment of adults with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy; [2] in ...
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