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Mutation analysis of 24 known cancer genes in the NCI-60 cell line set
Ikediobi, O.N., Edkins, S., Stevens, C., O'Meara, S., Bignell, G., Teague, J., Butler, A., Buck, G.,
Gray, K., Halliday, K., Kosmidou, V., Lugg, R., Menzies, A., Perry, J., Petty, R., Raine, K., Shepherd, R., Small, A.,
Widaa, S., Varian, J., Reinhold, W., Weinstein, J.N., Stratton, M.R., Futreal, P.A., and Wooster, R.
Mol Cancer Ther. 2006;5:2606-2612
Abstract:
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.
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