Co-Occurring Alterations in Multiple Tumor Suppressor Genes Are Associated With Worse Outcomes in Patients With EGFR-Mutant Lung Cancer.

Patients with metastatic EGFR-mutant NSCLC inevitably have disease progression while on tyrosine kinase inhibitor (TKI) therapy. Co-occurring tumor suppressor gene (TSG) alterations have been associated with poor outcomes, however, detailed analyses of their impact on patient outcomes are limited. Patients with EGFR-mutant NSCLC treated with EGFR TKIs who had tumor genomic profiling were included. Alterations in TP53 and five additional TSGs (RB1, NF1, ARID1A, BRCA1, and PTEN) were used to stratify the cohort into the following three subgroups: patients with tumors harboring a TP53 mutation plus a mutation in at least one additional TSG (TP53 A total of 101 patients from the Yale Cancer Center and 182 patients from the American Association for Cancer Research Project GENIE database were included. In the Yale cohort, TP53 mutations were identified in 65 cases (64%), of which 23 were TP53 Patients with TP53

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