BRAF is a serine/threonine kinase that plays a key role in the regulation of the mitogen-activated protein kinase (MAPK) cascade. Genetic alterations in BRAF are found in a large percentage of melanomas, thyroid cancers and histiocytic neoplasms as well as a small fraction of lung and colorectal cancers. Somatic mutations in BRAF have been found in up to 10% of all NSCLC, more common in adenocarcinomas. Genetic alterations of BRAF have been identified in 9% of lung adenocarcinomas. BRAF N581I lies within the protein kinase domain of the Braf protein (UniProt.org). N581I results in low Braf kinase activity and Ras-dependent activation of Erk signaling in cell culture but, induces similar cell proliferation and cell viability as wild-type Braf. The BRAF N581I mutation is known to be oncogenic.
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