biostudies-literatureTestoni ECancer Research UK105-16https://www.ebi.ac.uk/biostudies/studies/S-EPMC4734836biostudies-literatureUnknown8(2)The lack of actionable mutations in patients with non-small cell lung cancer (NSCLC) presents a significant hurdle in the design of targeted therapies for this disease. Here, we identify somatically mutated ABL1 as a genetic dependency that is required to maintain NSCLC cell survival. We demonstrate that NSCLC cells with ABL1 mutations are sensitive to ABL inhibitors and we verify that the drug-induced effects on cell viability are specific to pharmacological inhibition of the ABL1 kinase. Furthermore, we confirm that imatinib suppresses lung tumor growth in vivo, specifically in lung cancer cells harboring a gain-of-function (GOF) mutation in ABL1. Consistent with structural modeling, we demonstrate that mutations in ABL1 identified in primary NSCLC tumors and a lung cancer cell line incrEMBO molecular medicineSomatically mutated ABL1 is an actionable and essential NSCLC survival gene.PMC4734836129362046519278Stephenson NLTestoni EMorrow CJHudson ATrotter EWBrognard JMarusiak AATorres-Ayuso PHodgkinson CLDive CfalseSomatically mutated ABL1 is an actionable and essential NSCLC survival gene.The lack of actionable mutations in patients with non-small cell lung cancer (NSCLC) presents a significant hurdle in the design of targeted therapies for this disease. Here, we identify somatically mutated ABL1 as a genetic dependency that is required to maintain NSCLC cell survival. We demonstrate that NSCLC cells with ABL1 mutations are sensitive to ABL inhibitors and we verify that the drug-induced effects on cell viability are specific to pharmacological inhibition of the ABL1 kinase. Furthermore, we confirm that imatinib suppresses lung tumor growth in vivo, specifically in lung cancer cells harboring a gain-of-function (GOF) mutation in ABL1. Consistent with structural modeling, we demonstrate that mutations in ABL1 identified in primary NSCLC tumors and a lung cancer cell line incr2016-01-01T00:00:00Z2016 Feb2026-05-05T07:18:32.821Z2019-03-27T02:08:00ZS-EPMC47348362675868010.15252/emmm.201505456