KIT
小结
KIT是致癌基因，编码蛋白是3型跨膜受体酪氨酸激酶。KIT编码蛋白通过与其配体干细胞因子（SCF）结合后，受体通过二聚化和自磷酸化被激活。KIT活化导致通过几种途径（包括PI3K，MAPK和STAT）增加细胞内信号传导，最终导致细胞增殖和存活。80%-90%的GIST发生KIT激活突变，分布在多个外显子上，具有不同的频率：外显子11（66.1％），外显子9（13％），外显子13（1.2％）和外显子17（0.6％）。KIT基因的突变也与白血病、黑色素瘤、肥大细胞疾病有关。
The proto-oncogene KIT encodes a type 3 transmembrane receptor tyrosine kinase. The receptor is activated through dimerization and autophosphorylation upon binding by its ligand, stem cell factor (SCF) also known as mast cell growth factor (MGF). KIT activation results in increased intracellular signaling through several pathways including PI3K, MAPK and STAT, ultimately leading to cell proliferation and survival. For patients with wildtype gastrointestinal stromal tumors (GIST; no KIT or PDGFRA mutations), NCCN recommends testing for germline succinate dehydrogenase (SDH) mutations. About 10-15% of GISTs are wildtype; thus, the absence of a mutation does not exclude the diagnosis of GIST. In patients without KIT mutations, a subset of those with advanced GISTs benefit from imatinib (0-45% of patients). Activating KIT mutations occur in 80 - 90% of GISTs and are distributed over multiple exons with different frequencies (exons 11 (66.1%), exon 9 (13%), exon 13 (1.2%), and exon 17 (0.6%)). There are at least eight small molecule tyrosine kinase inhibitors (TKIs) targeting KIT that have been approved by the US Food and Drug Administration with the efficacy of each TKI strongly depending on the location of the activating KIT mutation.