title: A gene-alteration profile of human lung cancer cell lines.
abstract: Aberrant proteins encoded from genes altered in tumors drive cancer development and may also be therapeutic targets. Here we derived a comprehensive gene-alteration profile of lung cancer cell lines. We tested 17 genes in a panel of 88 lung cancer cell lines and found the rates of alteration to be higher than previously thought. Nearly all cells feature inactivation at TP53 and CDKN2A or RB1, whereas BRAF, MET, ERBB2, and NRAS alterations were infrequent. A preferential accumulation of alterations among histopathological types and a mutually exclusive occurrence of alterations of CDKN2A and RB1 as well as of KRAS, epidermal growth factor receptor (EGFR), NRAS, and ERBB2 were seen. Moreover, in non-small-cell lung cancer (NSCLC), concomitant activation of signal transduction pathways known to converge in mammalian target of rapamycin (mTOR) was common. Cells with single activation of ERBB2, PTEN, or MET signaling showed greater sensitivity to cell-growth inhibition induced by erlotinib, LY294002, and PHA665752, respectively, than did cells featuring simultaneous activation of these pathways, underlining the need for combined therapeutic strategies in targeted cancer treatments. In conclusion, our gene-alteration landscape of lung cancer cell lines provides insights into how gene alterations accumulate and biological pathways interact in cancer.
authors.affiliation: Lung Cancer Group, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Blanco
authors.forename: Reika
authors.initials: R
authors.lastname: Iwakawa
authors.forename: Moying
authors.initials: M
authors.lastname: Tang
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.forename: Barbara
authors.initials: B
authors.lastname: Angulo
authors.forename: Ruben
authors.initials: R
authors.lastname: Pio
authors.forename: Luis M
authors.initials: LM
authors.lastname: Montuenga
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
authors.forename: Montse
authors.initials: M
authors.lastname: Sanchez-Cespedes
mesh_terms: D000328:Adult; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction