High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.
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Abstract | Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo. |
Year of Publication | 2016
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Journal | Nat Biotechnol
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Volume | 34
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Issue | 4
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Pages | 419-23
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Date Published | 2016 Apr
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ISSN | 1546-1696
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URL | |
DOI | 10.1038/nbt.3460
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PubMed ID | 26928769
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Grant list | UL1DE019585 / DE / NIDCR NIH HHS / United States
U54CA112962 / CA / NCI NIH HHS / United States
RL1-GM084437 / GM / NIGMS NIH HHS / United States
Howard Hughes Medical Institute / United States
RL1-CA133834 / CA / NCI NIH HHS / United States
RL1-HG004671 / HG / NHGRI NIH HHS / United States
U54 CA112962 / CA / NCI NIH HHS / United States
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