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

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.

• Authors: 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 Kung, Todd R Golub
• Journal: Nature biotechnology (Nat Biotechnol) Vol. 34 Issue 4 Pg. 419-23 (Apr 2016) ISSN: 1546-1696 [Electronic] United States
• PMID: 26928769 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Cell Line, Tumor
• DNA Barcoding, Taxonomic (methods)
• Drug Resistance, Neoplasm (genetics)
• Genotyping Techniques (methods)
• High-Throughput Nucleotide Sequencing (methods)
• Humans
• Mice
• Neoplasms (classification, genetics)