The BRAF gene encodes a serine/threonine kinase protein involved in the mitogen-activated protein kinase signaling pathway (MAPKs). BRAF somatic mutations are found in approximately 15% of colorectal cancers (CRC)1,2 and approximately 45% of papillary thyroid carcinomas (PTC)3. The most common alteration of the BRAF gene is a thymidine to adenine change at nucleotide 1799, resulting in an amino acid change from valine to glutamic acid at codon 600 (V600E). This alteration has been shown to activate the kinase activity of the BRAF protein by simulating phosphorylation4.
The V600E BRAF mutation has been associated with resistance to Panitumumab or Cetuximab in metastatic colorectal cancer. One publication reported that none of their BRAF positive cases responded to therapy (p=0.029), and that these same individuals had a shorter progression-free survival (P=0.022) and overall survival (p<0.0001) compared to wild-type2. This mutation has also been associated with CRCs having high microsatellite instability, but not linked with Hereditary Nonpolyposis Colorectal Cancer (HNPCC)1,4, suggesting that V600E positive cases may not require testing of the mismatch repair genes associated with HNPCC (MLH1, MSH2, MSH6, and PMS2).
The vast majority of thyroid carcinomas are the papillary type. Disease recurrence after surgical treatment is common. The extent of initial surgical resection is determined by balancing the risks of recurrence with the risks of adverse outcomes, though reliable pre-operative indicators for recurrence have not been readily available. Recent studies have demonstrated a strong association with BRAF V600E and aggressive forms of primary PTC. One study found that BRAF V600E, detected by fine needle aspiration biopsy, strongly predicted extrathyroid extension (p=0.039), thyroid capsular invasion (p=0.045), and lymph node metastasis (p=0.002)5. Therefore, BRAF mutation status may provide additional information in prognosticating PTC’s and how aggressively they should be treated.
BRAF Gene, V600E Mutation Analysis Assay Summary
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References
1. Kadiyska, T. K. et al., (2007) Can Det and Prev; 31:254-256
2. Nicoloantonio, F. D. et al., (2009) J Clin Onc; 26:5705-5712
3.Chiosea, S. et al., (2009) Endo Path; 20:122-126
4. French, A. J. et al., (2008) Clin Can Res; 14:3408-3415
5. Xing, M. Et al., (2009) J Clin Onc; 27:2977-2982