What Is a BRAF Mutation? Which Cancers Can Be BRAF-Positive?

The BRAF gene encodes a protein with serine / threonine kinase activity involved in the intracellular mitogen-activated protein kinase signaling pathway (MAPKs). It controls cell division through KRAS. Somatic BRAF gene mutations are detected in malignant melanoma, colorectal cancer, and papillary thyroid cancer. The V600E mutation is most common.

The BRAF gene is located on the long arm of chromosome 7 (7q34) and contains 18 exons . Mutations are commonly found at codon 600 in exon 15 (V600A, V600D, V600E, and V600KRM) and in exon 11.

Although BRAF-mutated cancers generally behave more aggressively, studies suggest a much better prognosis in stage 4 colon and rectal cancer with non-V600 BRAF mutations. Therefore, the presence of a mutation alone should not determine interpretation; the codon in which it is located must also be considered.

FDA-approved drugs targeting BRAF mutations: vemurafenib (Zelboraf), dabrafenib (Tafinlar), trametinib (Mekinist), and cobimetinib (Cotellic)