Early-Stage Lung adenocarcinoma MDM2 genomic heterogeneity predicts clinical outcome and response to targeted therapy

Invasive subtypes of lung adenocarcinoma (LUAD) show MDM2 amplification that is associated with poor survival. Mouse double minute 2 (MDM2) is frequently amplified in lung adenocarcinoma (LUAD) and is a negative regulator of p53, which binds to p53 and regulates its activity and stability. Genomic amplification and overexpression of MDM2 together with genetic alterations in p53 leads to genomic and genetic heterogeneity in LUAD that represents a therapeutic target. In vitro assays in a panel of LUAD cell lines showed that tumor cell response to MDM2 targeted therapy is associated with MDM2 amplification. Transcriptomic analyses of MDM2 amplified LUAD cell lines with p53 WT(A549) and p53 mutant (H1792) treated with MDM2 inhibitor