Fig. 3: Driver variants conferring drug resistance.
From: Base editing screens define the genetic landscape of cancer drug resistance mechanisms
a, Base editing screens reveal clinically apparent hotspot mutations in oncogenes. Comparison of total COSMIC mutation counts for amino acid positions were compared with the z-score of gRNAs tiling across AKT1 and PIK3CA in HT-29 cells. b, Drug resistance variants to the PI3K inhibitor, pictilisib, in HT-29 cells. Comparison of gRNA z-scores for the control treated arm versus plasmid library, and the drug-treated arm versus plasmid library is shown. c, Drug resistance variants to the KRASG12C inhibitors, sotorasib and adagrasib, in H23 lung cancer cells. Comparison of gRNA z-scores for the sotorasib treated arm versus plasmid library, and the adagrasib treated arm versus plasmid library is shown. Predicted amino acid editing consequences are labeled for drug resistance variants. Data are the average of two independent screens performed on separate days.
