High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines
Nature biotechnology, 2016•nature.com
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 …
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 …
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.
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