학술논문
High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines
Document Type
article
Author
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
Source
Nature Biotechnology. 34(4)
Subject
Language
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.