{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Montuori G"],"funding":["National Institute of Neurological Disorders and Stroke","Deutsche Forschungsgemeinschaft (DFG)","Cancer Research UK","Berlin Institute of Health","Deutsche Krebshilfe","National Institute of Neurological Disorders and Stroke (NINDS)","Berlin Center for Machine Learning","UK Research and Innovation","Deutsche Krebshilfe (German Cancer Aid)","National Cancer Institute (NCI)","UK Research and Innovation (UKRI)","Berlin Institute of Health (BIH)","Berlin Center for Machine Learning (BZML)","European Research Council","Deutsche Forschungsgemeinschaft","National Cancer Institute","Chief Scientist Office","NINDS NIH HHS","NCI NIH HHS","Wellcome Trust"],"pagination":["2054-2077"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12456741"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(10)"],"pubmed_abstract":["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. Integrating theoretical models of oncogene copy number-dependent fitness with single-cell ecDNA quantification and phenotype analyses, we reveal that ecDNA copy-number heterogeneity drives phenotypic diversity and determines treatment sensitivity through mechanisms unattainable by chromosomal oncogene amplification. We demonstrate that ecDNA copy number directly influences cell fate "],"journal":["Cancer discovery"],"pubmed_title":["Extrachromosomal DNA-Driven Oncogene Dosage Heterogeneity Promotes Rapid Adaptation to Therapy in MYCN-Amplified Cancers."],"pmcid":["PMC12456741"],"funding_grant_id":["NS132780","MR/V02342X/1","CA030199","949172","R01 NS132780","398299703","70114107","Clinician Scientist Program","PCL/23/04","P30 CA030199","CRC1588","161L0222"],"pubmed_authors":["Gargiulo G","Rosenfeldt MT","Rodriguez-Fos E","Schmargon R","Koch A","Montuori G","Dorr JR","Mandal S","Krieger TG","Werner B","Henssen AG","Eggert A","Theißen J","Lehmann A","Gurgen D","Tu F","Dubois FPB","Kunkele A","Purshouse K","Schmitt MJ","Hui H","Spanjaard B","Buck V","Hundsdoerfer P","Taschner-Mandl S","Chavez L","Grunewald L","Huang W","Schallenberg S","Fischer M","Seyboldt H","Qin D","Helmsauer K","Bosco B","Fankhanel L","Coscia F"],"additional_accession":[]},"is_claimable":false,"name":"Extrachromosomal DNA-Driven Oncogene Dosage Heterogeneity Promotes Rapid Adaptation to Therapy in MYCN-Amplified Cancers.","description":"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. Integrating theoretical models of oncogene copy number-dependent fitness with single-cell ecDNA quantification and phenotype analyses, we reveal that ecDNA copy-number heterogeneity drives phenotypic diversity and determines treatment sensitivity through mechanisms unattainable by chromosomal oncogene amplification. We demonstrate that ecDNA copy number directly influences cell fate ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-06-04T06:54:21.62Z","creation":"2026-05-06T03:12:17.145Z"},"accession":"S-EPMC12456741","cross_references":{"pubmed":["40773595"],"doi":["10.1158/2159-8290.cd-24-1738","10.1158/2159-8290.CD-24-1738"]}}