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402714 | New Interpretation | 01/22/2019 1:34 PM |
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Tier 2InterpretationBRAF 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. E586 is located within the kinase domain of BRAF and E586K mutation has been shown to result in increased kinase activity. The BRAF E586K mutation is likely oncogenic although the predictive and prognostic significance of this mutation needs further study. Correlation with other laboratory and clinical findings is recommended.
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Citations- Wellbrock C, Karasarides M, Marais R. The RAF proteins take centre stage. Nat
- Rev Mol Cell Biol. 2004 Nov;5(11):875-85. Review.
- Davies H, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417(6892):949-54.
- Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014;511(7511):543-50.
- Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature 2012;489(7417):519-25.
- Wan PT, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 2004;116(6):855-67.
- Zheng G, et al. Clinical detection and categorization of uncommon and concomitant mutations involving BRAF. BMC Cancer 2015;15():779.
- Comprehensive TCGA PanCanAtlas (https://gdc.cancer.gov/about data/publications/pancanatlas).
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Last updated: 2019-01-22 18:34:45 UTC
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