Mutation analysis of 24 known cancer genes in the NCI-60 cell line set

被引:361
作者
Ikediobi, Ogechi N.
Davies, Helen
Bignell, Graham
Edkins, Sarah
Stevens, Claire
O'Meara, Sarah
Santarius, Thomas
Avis, Tim
Barthorpe, Syd
Brackenbury, Lisa
Buck, Gemma
Butler, Adam
Clements, Jody
Cole, Jennifer
Dicks, Ed
Forbes, Simon
Gray, Kristian
Halliday, Kelly
Harrison, Rachel
Hills, Katy
Hinton, Jonathan
Hunter, Chris
Jenkinson, Andy
Jones, David
Kosmidou, Vivienne
Lugg, Richard
Menzies, Andrew
Mironenko, Tatiana
Parker, Adrian
Perry, Janet
Raine, Keiran
Richardson, David
Shepherd, Rebecca
Small, Alex
Smith, Raffaella
Solomon, Helen
Stephens, Philip
Teague, Jon
Tofts, Calli
Varian, Jennifer
Webb, Tony
West, Sofie
Widaa, Sara
Yates, Andy
Reinhold, William
Weinstein, John N.
Stratton, Michael R.
Futreal, P. Andrew
Wooster, Richard
机构
[1] Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge CB10 1SA, England
[2] Natl Canc Inst, Mol Pharmacol Lab, Genom & Bioinformat Grp, Bethesda, MD USA
[3] Inst Canc Res, Sutton, Surrey, England
基金
英国惠康基金;
关键词
D O I
10.1158/1535-7163.MCT-06-0433
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The panel of 60 human cancer cell lines (the NCI-60) assembled by the National Cancer Institute for anticancer drug discovery is a widely used resource. The NCI-60 has been characterized pharmacologically and at the molecular level more extensively than any other set of cell lines. However, no systematic mutation analysis of genes causally implicated in oncogenesis has been reported. This study reports the sequence analysis of 24 known cancer genes in the NCI-60 and an assessment of 4 of the 24 genes for homozygous deletions. One hundred thirty-seven oncogenic mutations were identified in 14 (APC, BRAF, CDKN2, CTNNB1, HRAS, KRAS, NRAS, SMAD4, PIK3CA, PTEN, RB1, STK11, TP53, and VHL) of the 24 genes. All lines have at least one mutation among the cancer genes examined, with most lines (73%) having more than one. Identification of those cancer genes mutated in the NCI-60, in combination with pharmacologic and molecular profiles of the cells, will allow for more informed interpretation of anticancer agent screening and will enhance the use of the NCI-60 cell lines for molecularly targeted screens.
引用
收藏
页码:2606 / 2612
页数:7
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