(E) sgRNAs counts in tumors versus sgRNA detected in BRAFi-resistant cell library (in vitro) (respectively, black and orange points) for selected candidates. Each black point corresponds to one tumor. EGFR was the most potent BRAFi-resistant gene Two replicates have been shown for CRISPR-SAM cell library (orange points). SMAD3, BIRC3 and SLC9A5 were identified as hits in the three screens 