Genome-wide CRISPR Screen in a Mouse Model of Tumor Growth and Metastasis
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Zhang_Genome-wide.pdf
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Author(s)
Lee, Kyungheon
Song, Jun
Weissleder, Ralph
Lee, Hakho
Chen, Sidi
Sanjana, Neville E
Zheng, Kaijie
Shalem, Ophir
Shi, Xi
Scott, David Arthur
Date Issued
March 2015
Journal
Cell
Publisher
Elsevier
Citation
Chen, Sidi et al. “Genome-Wide CRISPR Screen in a Mouse Model of Tumor Growth and Metastasis.” Cell 160, 6 (March 2015): 1246–1260 © 2015 Elsevier Inc
Version
Author's final manuscript
Abstract
Genetic screens are powerful tools for identifying genes responsible for diverse phenotypes. Here we describe a genome-wide CRISPR/Cas9-mediated loss-of-function screen in tumor growth and metastasis. We mutagenized a non-metastatic mouse cancer cell line using a genome-scale library with 67,405 single-guide RNAs (sgRNAs). The mutant cell pool rapidly generates metastases when transplanted into immunocompromised mice. Enriched sgRNAs in lung metastases and late-stage primary tumors were found to target a small set of genes, suggesting that specific loss-of-function mutations drive tumor growth and metastasis. Individual sgRNAs and a small pool of 624 sgRNAs targeting the top-scoring genes from the primary screen dramatically accelerate metastasis. In all of these experiments, the effect of mutations on primary tumor growth positively correlates with the development of metastases. Our study demonstrates Cas9-based screening as a robust method to systematically assay gene phenotypes in cancer evolution in vivo.
MIT Department
Broad Institute of MIT and Harvard
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2015.02.038
