Acquired and constitutional genetic variations in cancers have a substantial influence on response to therapy. The NCI60 panel of cell lines provides a unique opportunity to investigate this problem. These 60 human tumor cell lines represent 9 cancer types, and are richly characterized as the result of many previous studies which have collected various biochemical and genomics data [1]. In addition, there exists a comprehensive dataset of sensitivity and resistance profiles of over 100,000 compounds with potential antineoplastic activity. However, characterization of coding region DNA sequence variants has been lacking. In this study, we sequenced the whole exomes of the NCI60 cell lines and identified single nucleotide variants and short insertions/deletions. Variants found by sequencing were in excellent agreement with variants previously identified by SNP analysis or targeted capillary sequencing. Even though most cell lines displayed similar mutation counts, cell lines with microsatellite instability displayed a hypermutator phenotype. In addition, observation from ti/tv ratio and nature of base changes revealed preservation of possible carcinogen specific DNA mutation signatures. Deleterious variants were identified at higher frequency in known cancer genes while TP53 mutations where the most frequent event among the NCI60. Finally, notable instances of correlation between gene/pathway mutations with sensitivity to certain drug/compounds was identified. For example, sensitivity to vemurafenib was highly correlated with BRAF mutation. This comprehensive dataset enhances the value of cell lines widely used as disease models in many laboratories by adding depth to the existing genomic data. Our analysis identifies a large number of genomic variants correlated with drug responsiveness, including a number of genes known to be targeted by specific agents as well as numerous candidates for future investigation. 1. Shankavaram, U.T., et al., CellMiner: a relational database and query tool for the NCI-60 cancer cell lines. BMC Genomics, 2009. 10: p. 277.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1879. doi:1538-7445.AM2012-1879