Identification of oncogenic driver mutations by genome-wide CRISPR-Cas9 dropout screening.

ABSTRACT:

Background

Genome-wide CRISPR-Cas9 dropout screens can identify genes whose knockout affects cell viability. Recent CRISPR screens detected thousands of essential genes required for cellular survival and key cellular processes; however discovering novel lineage-specific genetic dependencies from the many hits still remains a challenge.

Results

To assess whether CRISPR-Cas9 dropout screens can help identify cancer dependencies, we screened two human cancer cell lines carrying known and distinct oncogenic mutations using a genome-wide sgRNA library. We found that the gRNA targeting the driver mutation EGFR was one of the highest-ranking candidates in the EGFR-mutant HCC-827 lung adenocarcinoma cell line. Likewise, sgRNAs for NRAS and MAP2K1 (MEK1), a downstream kinase of mutan

SUBMITTER: Kiessling MK 

PROVIDER: S-EPMC5016932 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature