High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.
basic_science · Level V
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- Record sourced from PubMed, PMID 26928769.
- Also identified by DOI 10.1038/nbt.3460 and PMC identifier 5508574.
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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.
Medical subject headings
- DNA Barcoding, Taxonomic
- Drug Resistance, Neoplasm
- Genotyping Techniques
- High-Throughput Nucleotide Sequencing
- Neoplasms