title: PIK3CA mutations and copy number gains in human lung cancers.
abstract: 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.
authors.affiliation: Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, TX 75390-8593, USA.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Shigematsu
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nomura
authors.forename: William W
authors.initials: WW
authors.lastname: Lockwood
authors.forename: Mitsuo
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authors.lastname: Sato
authors.forename: Naoki
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authors.lastname: Okumura
authors.forename: Junichi
authors.initials: J
authors.lastname: Soh
authors.forename: Makoto
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authors.lastname: Suzuki
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Kwun M
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authors.lastname: Fong
authors.forename: Huei
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authors.lastname: Lee
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
authors.forename: Wan L
authors.initials: WL
authors.lastname: Lam
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Adi F
authors.initials: AF
authors.lastname: Gazdar