Multiple hotspot mutations of the BRAF gene including V600E
melanoma, thyroid cancer, colorectal cancer, lung cancer
The Oncology 48 gene Mutation Panel (Onco48) is designed to detect mutations within oncogenes and tumor suppressor genes frequently mutated in human cancers. Diagnostic, prognostic, and predictive biologic markers in this panel are important in personalizing cancer care. The result of this test may guide a patient to the appropriate chemotherapy or clinical trial. The Oncology Mutation Panel version The BRAF gene encodes a serine/threonine kinase protein involved in the mitogen-activated protein kinase signaling pathway (MAPKs). Somatic mutations of BRAF have been estimated to occur in up to ~15% of human tumors1,2. They are most commonly found in melanomas (~50%) and papillary thyroid carcinomas (PTC, ~45%)3 but are also known to occur in other cancers including colorectal cancers (CRC, ~15%)4, 5, and non-small cell lung cancer (NSCLC, ~4%)6. The most common BRAF mutation is the V600E change in exon 15 which has been shown to activate the kinase activity of BRAF by simulating phosphorylation7.
In malignant melanomas, BRAF V600E mutations have been strongly associated with sensitivity to BRAF inhibitor therapies8-11. Other studies have also associated BRAF mutation status with response to MEK inhibitors12-14.
Studies have demonstrated a strong association of BRAF V600E with aggressive forms of primary PTC5. Therefore, BRAF mutation status may provide additional information in prognosticating PTCs and how aggressively they should be treated.
In metastatic colorectal cancer (CRC), the V600E BRAF mutation has been associated with resistance to anti-EGFR therapies (panitumumab, cetuximab)4. This mutation has also been associated with CRCs having high microsatellite instability, but not in association with Lynch syndrome (Hereditary Nonpolyposis Colorectal Cancer, HNPCC)3,7, suggesting that V600E positive cases may not require testing of the mismatch repair genes associated with HNPCC (MLH1, MSH2, MSH6, and PMS2).
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BRAF-NGS (Targeted analysis for 77 cancer hotspot mutations (including V600E) in the BRAF gene by next generation sequencing.)
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- Patel SP, et al. Cancer. 2013 Feb 15;119(4):799-805.