PIK3CA mutation and amplification in human lung cancer
PIK3CA mutation and amplification in human lung cancer
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DOI：
10.1111/j.1440-1827.2007.02155.x
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发表时间：
2007-10-01
影响因子：
2.2
通讯作者：
Sugimura, Haruhiko
中科院分区：
文献类型：
--
作者：
Okudela, Koji;Suzuki, Masaya;Sugimura, Haruhiko
为了探讨磷脂酰肌醇-3-激酶，催化，α（PIK 3CA）在人类肺癌发生中的意义，研究了148例日本原发性肺癌患者的突变和拷贝数变化。为了生物学验证，在永生化的人气道上皮细胞系中研究了外源表达的野生型和突变的PIK 3CA的作用。在139名可用患者中的5名（3.6%）中发现了PIK 3CA突变，在115名患者中的21名（18.3%）中分别发现了拷贝数增加。总体而言，在两项分析结果均可用的106例患者中，有24例（22.6%）检测到突变或拷贝数增加。男性、吸烟者和鳞状细胞癌患者的拷贝数增加患病率高于相反类别的患者。拷贝数的变化显示在早期阶段的患病率较高的趋势（P = 0.038）。有趣的是，突变和拷贝数改变的存在在本患者中是相互排斥的，这意味着两者都具有同等的致癌潜力。过表达野生型PIK 3CA及其两种常见突变体K545 E和H1047 R均能显著增强永生化气道上皮16 HBE 140-细胞的贴壁非依赖性生长活性和迁移活性，但K545 E和H1047 R突变体的作用比野生型更为显著。目前证明了PIK 3CA在人类肺癌发生中的重要作用。
To explore the significance of phosphatidylinositol-3-kinase, catalytic, alpha (PIK3CA) in the carcinogenesis in human lung, mutations and copy number changes were investigated in 148 Japanese patients with primary cancer of the lung. For biological validation, the effects of exogenously expressed wild-type and mutated PIK3CA were studied in an immortalized human airway epithelial cell line. Mutations in PIK3CA were found in five (3.6%) of the 139 available patients, and copy number gains were found in 21 (18.3%) of 115 patients, respectively. Overall, mutations or copy number gains were detected in 24 of the 106 patients (22.6%) for whom results in both analyses were available. The prevalence of copy number gains was higher in men, smokers, and in patients with squamous cell carcinoma than in the opposite categories. The copy number changes showed a trend toward higher prevalence in the earlier stages (P = 0.038). Interestingly, the presence of mutations and of copy number alterations were mutually exclusive in the present patients, implying that both entail equivalent oncogenic potential. Over-expressed wild-type PIK3CA and its two common mutants, K545E and H1047R, significantly enhanced the anchorage-independent growth activity and migration activity of immortalized airway epithelium 16HBE14o- cells, but the effects of the K545E and H1047R mutants were more remarkable than those of the wild-type. The present demonstrates an important role of PIK3CA in human lung carcinogenesis.