PDGFRA
小结
PDGFRA是致癌基因，编码蛋白是血小板衍生生长因子α，是一种受体酪氨酸激酶。PDGFRA的细胞外结构域与其配体结合导致二聚化，进而导致受体的自身磷酸化和下游途径的激活（RAS-MAPK，PI3K和PLC-γ和细胞反应）。PDGFRA的突变（插入，缺失，融合和基因组扩增）导致其在几种肿瘤类型中的活化：约7％的胃肠道间质瘤（GIST）具有PDGFRA激活突变，并且这些突变与KIT突变相互排斥。据报道，~5％的中国黑色素瘤患者具有PDGFRA的激活突变；大约7-15％的胶质母细胞瘤（GBM）中检测到PDGFRA的扩增，是第二常见的受体酪氨酸激酶扩增，并且通常与框内缺失相关。在多种肿瘤类型中检测到PDGFRA的扩增和激活突变，例如非小细胞肺癌，慢性粒细胞白血病等肿瘤。
PDGFRA, a receptor tyrosine kinase, is altered by mutation, chromosomal rearrangement or amplifications in a diverse range of cancers.
The PDGFRA gene encodes for the protein Platelet-derived growth factor alpha (PDGFRA). Binding of ligand to the extracellular domain of PDGFRA, which contains immunoglobulin (Ig)-like domains, causes dimerization followed by autophosphorylation of the receptor and activation of downstream pathways such as RAS-MAPK, PI3K and PLC-γ that are involved in developmental and cellular responses. The catalytic activity of PDGFRA is mediated through the split intracellular tyrosine kinase domain; PDGFRA binds to all PDGF ligand isoforms except PDGF-DD. Mutations, insertions, deletions, fusions and genomic amplification of PDGFRA lead to its activation in several tumor types: ~7% of gastrointestinal stromal tumors (GISTs) have PDGFRA activating mutations and these mutations are mutually exclusive from KIT mutations; activating mutations in PDGFRA have been been reported in ~5% of Chinese melanoma patients; amplification of PDGFRA is the second most frequent receptor tyrosine kinase amplification in glioblastoma (GBM), is found in ~7-15% of GBM tumors and is often associated with in-frame deletions; amplification of the PDGFRA locus has been reported in more than 80% of intimal sarcomas, ~19% of malignant peripheral nerve sheath tumors, 3–7% of non-small cell lung adenocarcinomas and 8–10% non-small cell lung squamous cell carcinomas; activating mutations have been found in ~5% of diffuse intrinsic pontine gliomas and in ~14% of non-brain stem pediatric high-grade gliomas, around 40% of these occurring in the context of PDGFRA amplification; chimeric fusion transcripts to the catalytic domain of PDGFRA have been reported in select cases of GBM, chronic myeloid leukemia and hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL). PDGFRA mutations have also been reported in inflammatory fibroid polyps, and these mutations have been characterized as activating in other disease types.