Structural rearrangements generate cell-specific, gene-independent CRISPR-Cas9 loss of fitness effects.

ABSTRACT:

Background

CRISPR-Cas9 genome editing is widely used to study gene function, from basic biology to biomedical research. Structural rearrangements are a ubiquitous feature of cancer cells and their impact on the functional consequences of CRISPR-Cas9 gene-editing has not yet been assessed.

Results

Utilizing CRISPR-Cas9 knockout screens for 250 cancer cell lines, we demonstrate that targeting structurally rearranged regions, in particular tandem or interspersed amplifications, is highly detrimental to cellular fitness in a gene-independent manner. In contrast, amplifications caused by whole chromosomal duplication have little to no impact on fitness. This effect is cell line specific and dependent on the ploidy status. We devise a copy-number ratio metric that substantially im

SUBMITTER: Goncalves E 

PROVIDER: S-EPMC6362594 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature