show Abstracthide AbstractLarge panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous backbone upon which to study genetic variants, candidate targets, small molecule and biologic therapeutics and to identify new markers of cancer dependencies. Here we provide a substantial expansion of the CCLE to include genetic, epigenetic, miRNA, histone tail and protein-array characterization of 1,072 cell lines from various lineages and ethnicities (Figure 1, S1A; Supplementary Methods). We performed RNA sequencing (RNAseq, 1019 cell lines), whole exome sequencing (WES, 326), whole genome sequencing (WGS, 329), reverse phase protein array (RPPA, 899), reduced representation bisulfite sequencing (RRBS, 843), microRNA expression profiling (954) and global histone modification profiling (897) for CCLE cell lines. Integrating these data with functional characterization data, including drug sensitivities and gene dependencies, reveals potential new cancer drug targets and associated biomarkers. Together, this dataset and an accompanying public data portal provide a resource to accelerate cancer research using model cancer cell lines.