Edit ID | Edit Comment | Time | |
---|
402699 | New Interpretation | 01/22/2019 1:34 PM |
Before
The interpretation was not yet created, or had been deleted.After (Current Version)
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. 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.
|
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.
- Lito P, Rosen N, Solit DB. Tumor adaptation and resistance to RAF inhibitors.
- Nat Med. 2013 Nov;19(11):1401-9. doi: 10.1038/nm.3392. Review.
- Yao Z, Yaeger R, Rodrik-Outmezguine VS, Tao A, Torres NM, Chang MT, Drosten M, Zhao H, Cecchi F, Hembrough T, Michels J, Baumert H, Miles L, Campbell NM, de Stanchina E, Solit DB, Barbacid M, Taylor BS, Rosen N. Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS. Nature. 2017 Aug 10;548(7666):234-238.
- Ng PK, Li J, Jeong KJ, Shao S, Chen H, Tsang YH, Sengupta S, Wang Z, Bhavana
- VH, Tran R, Soewito S, Minussi DC, Moreno D, Kong K, Dogruluk T, Lu H, Gao J,
- Tokheim C, Zhou DC, Johnson AM, Zeng J, Ip CKM, Ju Z, Wester M, Yu S, Li Y,
- Vellano CP, Schultz N, Karchin R, Ding L, Lu Y, Cheung LWT, Chen K, Shaw KR,
- Meric-Bernstam F, Scott KL, Yi S, Sahni N, Liang H, Mills GB. Systematic
- Functional Annotation of Somatic Mutations in Cancer. Cancer Cell. 2018 Mar
- 12;33(3):450-462.e10.
|
Last updated: 2019-01-22 18:34:26 UTC
|