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Extrachromosomal DNA–Driven Oncogene Dosage Heterogeneity Promotes Rapid Adaptation to Therapy in MYCN -Amplified Cancers

7 Aug 2025

Abstract excerpt

Extrachromosomal DNA (ecDNA) amplification enhances intercellular oncogene dosage variability and accelerates tumor evolution by violating foundational principles of genetic inheritance through its asymmetric mitotic segregation. Spotlighting high-risk neuroblastoma, we demonstrate how ecDNA amplification undermines the clinical efficacy of current therapies in cancers with extrachromosomal MYCN amplification....

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PMID: 40773595
DOI: 10.1158/2159-8290.cd-24-1738

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