Abstract 7511: Extrachromosomal MDM2 amplifications define an ecDNA-permissive tumor cell state that impacts intercellular tumor heterogeneity and treatment response across cancers

Key Points

• To explore how MDM2 ecDNA amplifications affect tumor heterogeneity and treatment responses in various cancers, particularly in TP53-wildtype tumors.
• Integrated analysis of pan-cancer ecDNA reconstructions
• Single-cell DNA and RNA sequencing
• Acute drug treatment perturbations in cell lines and PDX models
• Fluorescence-in-situ hybridization and immunofluorescence
• MDM2 is the most frequently amplified oncogene across cancers on ecDNA.
• MDM2 ecDNA is linked to increased copy number and complexity, especially in TP53-wildtype tumors.
• Treatment responses varied significantly based on MDM2 ecDNA levels, impacting TP53 activity and cell survival.

Abstract