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The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available1. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens2.
Human cancer cell lines represent a mainstay of tumour biology and drug discovery through facile experimental manipulation, global and detailed mechanistic studies, and various high-throughput applications. Numerous studies have used cell-line panels annotated with both genetic and pharmacological data, either within a tumour lineage3-5 or across multiple cancer types6-12. Although affirming the promise of systematic cell line studies, many previous efforts were limited in their depth of genetic characterization and pharmacological interrogation.
To address these challenges, we generated a large-scale genomic data set for 947 human cancer cell lines, together with pharmacological profiling of 24 compounds across ,500 of these lines. The resulting collection, which we termed the Cancer Cell Line Encyclopedia (CCLE), encompasses 36 tumour types (Fig. 1a and Supplementary Table 1; see also http://www.broadinstitute.org/ccle).All cell lineswere characterized by several genomic technology platforms. The mutational status of .1,600 genes was determined by targetedmassively parallel sequencing, followed by removal of variants likely to be germline events (Supplementary Methods). Moreover, 392 recurrent mutations affecting 33 known cancer genes were assessed by mass spectrometric genotyping13 (Supplementary Table 2 and Supplementary Fig. 1). DNA copy number wasmeasured using high-density single nucleotide polymorphism arrays...