BACKGROUND AND CLINICAL SIGNIFICANCE
BRAF is a human gene encoding the protein, B-Raf, a serine/threonine-protein kinase which plays a role in regulating the MAP kinase/ERKs signaling pathway and affects cell division, differentiation, and secretion. Activating mutations of BRAF are known to be involved in several human cancers.
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 > 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. In 90% of the cases, thymine is substituted with adenine at nucleotide 1799, leading to an amino acid change from valine (V) to glutamate (E) at codon 600 or “V600E” in the activation segment of the protein. This mutation has been widely observed in thyroid carcinoma, colorectal cancer, melanoma and non-small-cell lung cancer. In 2011, a large-scale next-generation sequencing effort identified V600E as a likely driver mutation in 100% of cases of hairy cell leukaemia.
The antitumor efficacy resulting from RAF pathway inhibition has led to the development of specific inhibitors of mutated B-raf protein for anticancer use. One example is Vemurafenib (RG7204), which was approved by the US Food and Drug Administration as Zelboraf for the treatment of metastatic melanoma in 2011. Other B-raf inhibitors include GDC-0879, PLX-4720, and Sorafenib Tosylate (Nexavar) targeting melanoma, colorectal and renal cancers.
BRAF ASSAY DESCRIPTION
Next-generation-sequencing-based analysis of exon 1, encompassing positions 1,330-1814 and covering 54 known mutations in the BRAF gene. Sample types for mutation analysis include:
Formalin-Fixed, Paraffin-Embedded Tumor Tissue
+ 40-80 um total section thickness, ≥ 20% tumor
+ Shipped overnight, room temperature
+ 5-25 mg
+ Shipped overnight, frozen, on dry ice
+ 5-10 ml Blood in EDTA purple-top tube(s)