We identified for the first time a selection of three cancer driver mutations (P53, KRAS and VHL) during CRISPR-Cas9 gene editing and chart a comprehensive gene-wise editing risk map in our new work out today. This series summarizes it 1/X biorxiv.org/content/biorxi…
Recent reports in @NatureMedicine suggested that CRISPR-Cas9 gene editing induces a p53-dependent DNA damage response in primary cells, which may select for cells with oncogenic p53 mutations. These CRISPR-induced possible changes needs a systematic and thorough testing. 2/X 
Leveraging computational and experimental techniques we asked whether CRISPR gene editing may select for other oncogenic mutations and if yes, which genes editing could severely induce this selection. 3/X
We analyzed genome-wide CRISPR and RNAi screens @CancerDepMap to systematically chart the mutation selection potential of CRISPR knockouts across the whole exome. 4/X
@CancerDepMap Our analysis suggests that CRISPR gene editing can select for mutants of KRAS and VHL, at a level comparable to that reported for p53. 5/X
We found that the genes in the fragile region of the genome are highly likely to induce a strong mutation selection due to severe DNA damage response. 6/X
Finally, we performed a pooled and arrayed CRISPR screens to evaluate the competition between CRISPR-edited isogenic p53 WT and mutant cell lines, testifying our findings by showing a growth of p53 mutants over Wild type in a co-culture. 8/X
Our findings suggest a cautionary monitoring of these three driver genes status during the usage of CRISPR-Cas9 for cell-based therapy, especially while editing a set of genes at a high risk for inducing mutation selection identified and provided in our work. 9/X @Sanjusinha7
@Sanjusinha7 Kudos to our team @Sanjusinha7 @cheng_ky @joo_sang_lee and our amazing collaborators @thedeshpandelab, Karina Barbosa and @ZeevRonai. Further, Brid Ryan from LHC @NCIResearchCtr and @maxleiserson from @UMDCBCB
