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

作者：Ogechi N. Ikediobi, Helen Ruth Davies, Graham R. Bignell, Sarah Edkins, Claire Stevens, Sarah O’Meara, Thomas Santarius, Tim Avis, Syd Barthorpe, Lisa Brackenbury, Gemma Buck, Adam P. Butler, Jody Clements, Jennifer M. Cole, Ed Dicks, Simon Andrew Forbes, Kristian A. Gray, Kelly Halliday, Rachel Harrison, Katy Hills, Jonathan Hinton, Chris Hunter, Andy Jenkinson, David Jones, Vivienne Kosmidou, Richard Lugg, Andrew H. Menzies, Tatiana Mironenko, Adrian G. Parker, Janet Perry, Keiran M. Raine, David Richardson, Rebecca F. Shepherd, Alex Small, Raffaella Smith, Helen Solomon, Philip Stephens, Jon W. Teague, Calli Tofts, Jennifer Varian, Tony Webb, Sofie West, Sara Widaa, Andy Yates, William C. Reinhold, John N. Weinstein, Michael R. Stratton, P. Andrew Futreal, Richard Wooster · 发表于：Molecular Cancer Therapeutics · 年份：2006 · DOI：10.1158/1535-7163.mct-06-0433 · 被引用次数：445 · 研究领域：Lung Cancer Treatments and Mutations、Cancer-related Molecular Pathways、Cancer Genomics and Diagnostics

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.