A genetic interaction analysis identifies cancer drivers that modify EGFR dependency

摘要: A large number of cancer drivers have been identified through tumor sequencing efforts, but how they interact and the degree to which can substitute for each other not systematically explored. To comprehensively investigate genetically interact, we searched modifiers epidermal growth factor receptor (EGFR) dependency by performing CRISPR, shRNA, expression screens in a non-small cell lung (NSCLC) model. We elucidated broad spectrum suppressor genes (TSGs) oncogenes (OGs) that modify proliferation survival cells when EGFR signaling is altered. These include already known mediate inhibitor resistance as well many TSGs previously connected whose biological functions tumorigenesis are understood. show mutation PBRM1, subunit SWI/SNF complex, attenuates effects inhibition part sustaining AKT signaling. also Capicua (CIC), transcriptional repressor, suppresses partially restoring EGFR-promoted gene program, including sustained Ets transcription factors such ETV1 Together, our data provide strong support hypothesis certain contexts broaden understanding regulation.