Oncogenic mutations of PIK3CA in human cancers
Oncogenic mutations of PIK3CA in human cancers
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DOI：
10.4161/cc.3.10.1164
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发表时间：
2004-10-01
期刊：
影响因子：
4.3
通讯作者：
Velculescu, VE
中科院分区：
文献类型：
--
作者：
Samuels, Y;Velculescu, VE
磷脂酰肌醇 3-激酶 (PI3K) 是信号通路的重要调节因子。为了确定 PI3K 在人类癌症中是否发生基因改变，我们最近分析了 PI3K 基因家族的序列，发现编码 p110α 催化亚基的 PIK3CA 基因这一成员在结肠癌、乳腺癌、脑癌和肺癌中经常发生突变。大多数突变聚集在 PI3K 螺旋或催化结构域内的两个位置附近，并且至少一个热点突变似乎增加了激酶活性。 PIK3CA 代表人类癌症中发现的突变程度最高的癌基因之一，可能是有用的诊断和治疗靶点。
Phosphatidylinositol 3-kinases (PI3Ks) are important regulators of signaling pathways. To determine whether PI3Ks are genetically altered in human cancers, we recently analyzed the sequences of the PI3K gene family and discovered that one member, the PIK3CA gene encoding the p110alpha catalytic subunit, was frequently mutated in cancers of the colon, breast, brain and lung. The majority of mutations clustered near two positions within the PI3K helical or catalytic domains and at least one hotspot mutation appeared to increase kinase activity. PIK3CA represents one of the most highly mutated oncogenes identified in human cancers and may be a useful diagnostic and therapeutic target.