A Gene-Alteration Profile of Human Lung Cancer Cell Lines

被引：107

作者：

Blanco, Raquel ^{[1
]}

Iwakawa, Reika ^{[2
]}

Tang, Moying ^{[1
]}

Kohno, Takashi ^{[2
]}

Angulo, Barbara ^{[1
]}

Pio, Ruben ^{[3
]}

Montuenga, Luis M. ^{[3
]}

Minna, John D. ^{[4
]}

Yokota, Jun ^{[2
]}

Sanchez-Cespedes, Montse ^{[1
]}

机构：

[1] CNIO, Mol Pathol Programme, Lung Canc Grp, Madrid, Spain

[2] Natl Canc Ctr, Res Inst, Div Biol, Tokyo 104, Japan

[3] Univ Navarra, CIMA, Div Oncol, E-31080 Pamplona, Spain

[4] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA

来源：

HUMAN MUTATION | 2009年 / 30卷 / 08期

关键词：

lung cancer; oncogenes; tumor suppressors; tyrosine kinase inhibitors; HUMAN RETINOBLASTOMA GENE; P53; GENE; RAS MUTATIONS; RB PROTEIN; K-RAS; INACTIVATION; CARCINOMA; EXPRESSION; SUBSET; OVEREXPRESSION;

D O I：

10.1002/humu.21028

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 an-tong 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, 1199-1206, 2009. (C) 2009 Wiley-Liss, Inc.

引用

页码：1199 / 1206

页数：8

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