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

Channing Yu, Aristotle M. Mannan, Griselda Metta Yvone, Kenneth N. Ross, Yan Ling Zhang, Melissa A. Marton, Bradley R. Taylor, Andrew Crenshaw, Joshua Z. Gould, Pablo Tamayo, Barbara A. Weir, Aviad Tsherniak, Bang Wong, Levi A. Garraway, Alykhan F. Shamji, Michelle A. Palmer, Michael A. Foley, Wendy Winckler, Stuart L. Schreiber, Andrew L. KungTodd R. Golub

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)419-423
Number of pages5
JournalNature Biotechnology
Volume34
Issue number4
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Biotechnology
  • Molecular Medicine
  • Bioengineering
  • Biomedical Engineering

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    Yu, C., Mannan, A. M., Yvone, G. M., Ross, K. N., Zhang, Y. L., Marton, M. A., Taylor, B. R., Crenshaw, A., Gould, J. Z., Tamayo, P., Weir, B. A., Tsherniak, A., Wong, B., Garraway, L. A., Shamji, A. F., Palmer, M. A., Foley, M. A., Winckler, W., Schreiber, S. L., ... Golub, T. R. (2016). High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines. Nature Biotechnology, 34(4), 419-423. https://doi.org/10.1038/nbt.3460