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 nonsmall-
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, 1199–1206, 2009. & 2009Wiley-Liss, Inc.