A systematic genome-wide mapping of oncogenic mutation selection during CRISPR-Cas9 genome editing.

ABSTRACT: Recent studies have reported that genome editing by CRISPR-Cas9 induces a DNA damage response mediated by p53 in primary cells hampering their growth. This could lead to a selection of cells with pre-existing p53 mutations. In this study, employing an integrated computational and experimental framework, we systematically investigated the possibility of selection of additional cancer driver mutations during CRISPR-Cas9 gene editing. We first confirm the previous findings of the selection for pre-existing p53 mutations by CRISPR-Cas9. We next demonstrate that similar to p53, wildtype KRAS may also hamper the growth of Cas9-edited cells, potentially conferring a selective advantage to pre-existing KRAS-mutant cells. These selective effects are widespread, extending across cell-types and metho

SUBMITTER: Sinha S 

PROVIDER: S-EPMC8586238 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature