To investigate whether pooled whole-genome CRISPR-Cas9 screening is an appropriate means to identify oncogenic drivers and novel dependencies we selected two human cancer cell lines with known mutations: (1) the neuroblastoma-derived cell line CHP-212, which carries a RAS (NRAS) Q61K mutation and is highly sensitive to MEK inhibitors [12, 13]; (2) the lung cancer cell line HCC-827, which carries a deletion in the epidermal growth factor receptor (EGFR) delE746 and is sensitive to EGFR inhibitors including Gefitinib and Erlotinib [14]. Here, EGFR is linked to lung carcinoma.