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High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines
- Yu, Channing;
- Mannan, Aristotle M;
- Yvone, Griselda Metta;
- Ross, Kenneth N;
- Zhang, Yan-Ling;
- Marton, Melissa A;
- Taylor, Bradley R;
- Crenshaw, Andrew;
- Gould, Joshua Z;
- Tamayo, Pablo;
- Weir, Barbara A;
- Tsherniak, Aviad;
- Wong, Bang;
- Garraway, Levi A;
- Shamji, Alykhan F;
- Palmer, Michelle A;
- Foley, Michael A;
- Winckler, Wendy;
- Schreiber, Stuart L;
- Kung, Andrew L;
- Golub, Todd R
- et al.
Published Web Location
https://doi.org/10.1038/nbt.3460Abstract
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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