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Nat Biotechnol DOI:10.1038/nbt.3460

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

Publication TypeJournal Article
Year of Publication2016
AuthorsYu, C, Mannan, AM, Yvone, GMetta, Ross, KN, Zhang, Y-L, Marton, MA, Taylor, BR, Crenshaw, A, Gould, JZ, Tamayo, P, Weir, BA, Tsherniak, A, Wong, B, Garraway, LA, Shamji, AF, Palmer, MA, Foley, MA, Winckler, W, Schreiber, SL, Kung, AL, Golub, TR
JournalNat Biotechnol
Date Published2016 Apr
KeywordsAnimals, Cell Line, Tumor, DNA Barcoding, Taxonomic, Drug Resistance, Neoplasm, Genotyping Techniques, High-Throughput Nucleotide Sequencing, Humans, Mice, Neoplasms

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.


Alternate JournalNat. Biotechnol.
PubMed ID26928769
Grant ListUL1DE019585 / DE / NIDCR NIH HHS / United States
U54CA112962 / CA / NCI NIH HHS / United States
RL1-GM084437 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
RL1-CA133834 / CA / NCI NIH HHS / United States
RL1-HG004671 / HG / NHGRI NIH HHS / United States
U54 CA112962 / CA / NCI NIH HHS / United States