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. There has not, however, been a systematic sequence analysis of the NCI-60 for key genes causally implicated in oncogenesis. Therefore, we sequenced the exons and exon-intron boundaries of 32 known cancer genes in 59 of the cell lines (the sixtieth being unavailable at the time of the study). Thirteen of the 32 genes contain likely disease-causing mutations: TP53, BRAF, KRAS, HRAS, NRAS, PIK3CA, APC, CTNNB1, RB1, MADH4, STK11, PTEN and CDKN2A. All of the cell lines have at least one mutation in the cancer genes examined, with 60% (35/59) having more than one. The mutation patterns in the cell lines reflect the known mutation spectra in primary tumors from the respective tissue of origin. Knowledge of the genetic aberrations at the level of DNA sequence, in combination with the pharmacological and other molecular profiles of the cells, will better direct their future use in making genotype-to-phenotype correlates with response to chemotherapy.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]