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High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.

  • Author(s): 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.3460
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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