Cancer Cell Line Encyclopedia (Broad/Novartis)

Overview

The Cancer Cell Line Encyclopedia (CCLE) is a large-scale genomic and pharmacologic resource developed jointly by the Broad Institute and Novartis Institutes for BioMedical Research. It profiles 947 human cancer cell lines spanning 36 tumor lineages with multi-omic data — targeted massively parallel sequencing, copy number, gene expression, and mass spectrometric genotyping — coupled with pharmacologic profiling of 24 anticancer drugs across 479-481 lines using 8-point dose-response curves.

Composition

Assays / panels (linked)

  • Targeted massively parallel sequencing of >1,600 genes.
  • OncoMap: mass spectrometric genotyping (Sequenom genotyping) of 492 mutations in 33 cancer genes.
  • Affymetrix SNP 6.0 copy number arrays.
  • Affymetrix U133 Plus 2.0 expression arrays.
  • Pharmacologic profiling: 8-point dose-response curves.

Papers using this cohort

  • PMID:22460905 — Primary CCLE publication describing the resource and pharmacogenomic findings.
  • PMID:24686850 — Lin et al. (2014): CCLE cell-line expression data used to cross-reference ZNF750 mRNA expression in the context of ESCC genomic characterization.
  • PMID:28196596 — Gardner et al. 2017, Cancer Cell: CCLE bi-modal SLFN11 expression data used to validate that SLFN11 expression is lower in SCLC cell lines derived from previously-treated patients.

Notable findings derived from this cohort

  • EGFR mutations predict erlotinib sensitivity; ERBB2 amplification/overexpression predicts lapatinib sensitivity; BRAF V600E predicts sensitivity to RAF inhibitors PLX4720 and RAF265 PMID:22460905.
  • SLFN11 expression is the top correlate of irinotecan and topotecan sensitivity across 12 of 16 lineages; all three Ewing sarcoma lines tested were sensitive to irinotecan PMID:22460905.
  • AHR expression correlates with MEK inhibitor sensitivity in NRAS-mutant cancer cell lines; functional dependency confirmed by shRNA knockdown PMID:22460905.
  • 12 of 14 multiple myeloma (PCM) cell lines showed enhanced sensitivity to the IGF-1R inhibitor AEW541, with high IGF1 and IGF1R expression PMID:22460905.
  • Hematologic lineages showed preferential sensitivity to panobinostat (HDAC inhibitor) PMID:22460905.
  • Elastic net regression across >50,000 genomic features was used to build predictive models of drug sensitivity PMID:22460905.
  • ZNF750 mRNA expression referenced from CCLE cell-line data as part of ESCC tumor-versus-normal expression comparisons PMID:24686850.
  • SLFN11 expression analyzed across CCLE SCLC cell lines to confirm bimodal distribution; lower expression in lines derived from previously-treated patients (p=0.031), supporting SLFN11 as a treatment-experience-dependent biomarker in SCLC PMID:28196596.

Sources

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