PIK3CA mutation and amplification in human lung cancer
- 30 August 2007
- journal article
- Published by Wiley in Pathology International
- Vol. 57 (10), 664-671
- https://doi.org/10.1111/j.1440-1827.2007.02155.x
Abstract
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.Keywords
This publication has 26 references indexed in Scilit:
- PIK3CA mutation status in Japanese lung cancer patientsLung Cancer, 2006
- PTEN and PIK3CA Expression Is Associated with Prolonged Survival after Gefitinib Treatment in EGFR-Mutated Lung Cancer PatientsJournal of Thoracic Oncology, 2006
- Repeated fluorescence in situ hybridization by a microwave-enhanced protocolPathology International, 2006
- Human Tumor Mutants in PI3K p110α SubunitCell Cycle, 2006
- Chromosomal numerical abnormalities in early stage lung adenocarcinomaPathology International, 2006
- Mutation of the PIK3CA oncogene in human cancersBritish Journal of Cancer, 2006
- PIK3CA mutation and histological type in breast carcinoma: high frequency of mutations in lobular carcinomaThe Journal of Pathology, 2005
- A screen of the complete protein kinase gene family identifies diverse patterns of somatic mutations in human breast cancerNature Genetics, 2005
- Oncogenic Mutations of PIK3CA in Human CancersCell Cycle, 2004
- K-ras Gene Mutation Enhances Motility of Immortalized Airway Cells and Lung Adenocarcinoma Cells via Akt Activation: Possible Contribution to Non-Invasive Expansion of Lung AdenocarcinomaThe American Journal of Pathology, 2004