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A gene‐alteration profile of human lung cancer cell lines
Author(s) -
Blanco Raquel,
Iwakawa Reika,
Tang Moying,
Kohno Takashi,
Angulo Barbara,
Pio Ruben,
Montuenga Luis M.,
Minna John D.,
Yokota Jun,
SanchezCespedes Montse
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21028
Subject(s) - biology , kras , pten , neuroblastoma ras viral oncogene homolog , cancer research , lung cancer , erlotinib , cdkn2a , epidermal growth factor receptor , pi3k/akt/mtor pathway , cancer , signal transduction , cancer cell , gene signature , gefitinib , egfr inhibitors , gene , microbiology and biotechnology , genetics , pathology , gene expression , colorectal cancer , medicine
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. Hum Mutat 30,1–8, 2009. © 2009 Wiley‐Liss, Inc.