PIK3CA mutations and copy number gains in human lung cancers

Hiromasa Yamamoto, Hisayuki Shigematsu, Masaharu Nomura, William W. Lockwood, Mitsuo Sato, Naoki Okumura, Junichi Soh, Makoto Suzuki, Ignacio I. Wistuba, Kwun M. Fong, Huei Lee, Shinichi Toyooka, Hiroshi Date, Wan L. Lam, John D. Minna, Adi F. Gazdar

研究成果: 雜誌貢獻文章

316 引文 斯高帕斯(Scopus)

摘要

We investigated the frequency and function of mutations and increased copy number of the PIK3CA gene in lung cancers. PIK3CA 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 PIK3CA 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 PIK3CA alterations and mutational status of epidermal growth factor receptor (EGFR) signaling pathway genes (EGFR, KRAS, HER2, and BRAF). We also determined PIK3CA 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. PIK3CA 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 PIK3CA was not mutually exclusive to EGFR or KRAS. PIK3CA 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 PIK3CA mutations or gains but was not effective in PIK3CA wild-type cells. PIK3CA mutations or gains are present in a subset of lung cancers and are of functional importance.
原文英語
頁(從 - 到)6913-6921
頁數9
期刊Cancer Research
68
發行號17
DOIs
出版狀態已發佈 - 九月 1 2008
對外發佈Yes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Yamamoto, H., Shigematsu, H., Nomura, M., Lockwood, W. W., Sato, M., Okumura, N., Soh, J., Suzuki, M., Wistuba, I. I., Fong, K. M., Lee, H., Toyooka, S., Date, H., Lam, W. L., Minna, J. D., & Gazdar, A. F. (2008). PIK3CA mutations and copy number gains in human lung cancers. Cancer Research, 68(17), 6913-6921. https://doi.org/10.1158/0008-5472.CAN-07-5084