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

Nat Biotechnol
Authors
Keywords
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.

Year of Publication
2016
Journal
Nat Biotechnol
Volume
34
Issue
4
Pages
419-23
Date Published
2016 Apr
ISSN
1546-1696
URL
DOI
10.1038/nbt.3460
PubMed ID
26928769
Links
Grant list
UL1DE019585 / 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