PIK3CA mutation and amplification in human lung cancer
Article first published online: 30 AUG 2007
Volume 57, Issue 10, pages 664–671, October 2007
How to Cite
Okudela, K., Suzuki, M., Kageyama, S., Bunai, T., Nagura, K., Igarashi, H., Takamochi, K., Suzuki, K., Yamada, T., Niwa, H., Ohashi, R., Ogawa, H., Mori, H., Kitamura, H., Kaneko, T., Tsuneyoshi, T. and Sugimura, H. (2007), PIK3CA mutation and amplification in human lung cancer. Pathology International, 57: 664–671. doi: 10.1111/j.1440-1827.2007.02155.x
- Issue published online: 30 AUG 2007
- Article first published online: 30 AUG 2007
- Received 1 April 2007. Accepted for publication 8 June 2007.
- lung cancer;
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.