Data from <i>PIK3CA</i> Mutations and Copy Number Gains in Human Lung Cancers

Abstract

<div>Abstract<p>We investigated the frequency and function of mutations and increased copy number of the <i>PIK3CA</i> gene in lung cancers. <i>PIK3CA</i> mutations are one of the most common gene changes present in human cancers. We analyzed the mutational status of exons 9 and 20 and gene copy number of <i>PIK3CA</i> using 86 non–small cell lung cancer (NSCLC) cell lines, 43 small cell lung cancer (SCLC) cell lines, 3 extrapulmonary small cell cancer (ExPuSC) cell lines, and 691 resected NSCLC tumors and studied the relationship between <i>PIK3CA</i> alterations and mutational status of epidermal growth factor receptor (EGFR) signaling pathway genes (<i>EGFR, KRAS, HER2</i>, and <i>BRAF</i>). We also determined <i>PIK3CA</i> expression and activity and correlated the findings with effects on cell growth. We identified mutations in 4.7% of NSCLC cell lines and 1.6% of tumors of all major histologic types. Mutations in cell lines of small cell origin were limited to two ExPuSC cell lines. <i>PIK3CA</i> copy number gains were more frequent in squamous cell carcinoma (33.1%) than in adenocarcinoma (6.2%) or SCLC lines (4.7%). Mutational status of <i>PIK3CA</i> was not mutually exclusive to <i>EGFR</i> or <i>KRAS. PIK3CA</i> alterations were associated with increased phosphatidylinositol 3-kinase activity and phosphorylated Akt expression. RNA interference–mediated knockdown of PIK3CA inhibited colony formation of cell lines with <i>PIK3CA</i> mutations or gains but was not effective in <i>PIK3CA</i> wild-type cells. <i>PIK3CA</i> mutations or gains are present in a subset of lung cancers and are of functional importance. [Cancer Res 2008;68(17):6913–21]</p></div>