{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Noorani I"],"funding":["Cancer Research UK","Royal Society","UK Research and Innovation","Royal Society (The Royal Society)","Mark Foundation For Cancer Research (The Mark Foundation for Cancer Research)","National Cancer Institute (NCI)","UK Research and Innovation (UKRI)","European Research Council","Barts Charity","Medical Research Council","Mark Foundation For Cancer Research","National Cancer Institute","Novo Nordisk Foundation Center for Basic Metabolic Research","NCI NIH HHS","Wellcome Trust","NIGMS NIH HHS","Novo Nordisk Foundation Center for Basic Metabolic Research (NovoNordisk Foundation Center for Basic Metabolic Research)"],"pagination":["2078-2095"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12498097"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(10)"],"pubmed_abstract":["Oncogenes amplified on extrachromosomal DNA (ecDNA) contribute to treatment resistance and poor survival across cancers. Currently, the spatiotemporal evolution of ecDNA remains poorly understood. In this study, we integrate computational modeling with samples from 94 treatment-naive human glioblastomas (GBM) to investigate the spatiotemporal evolution of ecDNA. We observe oncogene-specific patterns of ecDNA spatial heterogeneity, emerging from random ecDNA segregation and differing fitness advantages. Unlike PDGFRA-ecDNAs, EGFR-ecDNAs often accumulate prior to clonal expansions, conferring strong fitness advantages and reaching high abundances. In corroboration, we observe pretumor ecDNA accumulation in vivo in genetically engineered mouse neural stem cells. Variant and wild-type EGFR-ecD"],"journal":["Cancer discovery"],"pubmed_title":["Extrachromosomal DNA-Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma."],"pmcid":["PMC12498097"],"funding_grant_id":["835297","NIH K00CA274692","R01-GM114362","MR/V02342X/1","NIH K99CA286968","P30 CA008748","21-029-ASP","U24 CA264379","OT2 CA278635","ID16584","OT2CA278635","FC001169","U24-CA264379","CGCATF-2021/100025","MGU045","K00 CA274692","OT2 CA278688","R01 GM114362","OT2CA278688","C416/A21999","RP/EA/180007","C11496/A17786","C11496/A30025","R01 CA282913","K99 CA286968","CGCATF-2021/100012"],"pubmed_authors":["Norton EJ","Bailey C","Swanton C","Fabian M","Nicoll JAR","Haughey M","Joo E","Ventura A","Terenzi F","Lisi M","Mischel PS","Weeden CE","Werner B","Santarius T","Nye EL","Boche D","Wong IT","Jones MG","Sharma N","Bafna V","Noorani I","Kittel J","Chang HY","Rowan A","Kanu N","Pradella D","Gronroos E","Green M","Meader L","Jamal-Hanjani M","Huang W","Luebeck J","Barbe V","Bell DM","Hung KL"],"additional_accession":[]},"is_claimable":false,"name":"Extrachromosomal DNA-Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma.","description":"Oncogenes amplified on extrachromosomal DNA (ecDNA) contribute to treatment resistance and poor survival across cancers. Currently, the spatiotemporal evolution of ecDNA remains poorly understood. In this study, we integrate computational modeling with samples from 94 treatment-naive human glioblastomas (GBM) to investigate the spatiotemporal evolution of ecDNA. We observe oncogene-specific patterns of ecDNA spatial heterogeneity, emerging from random ecDNA segregation and differing fitness advantages. Unlike PDGFRA-ecDNAs, EGFR-ecDNAs often accumulate prior to clonal expansions, conferring strong fitness advantages and reaching high abundances. In corroboration, we observe pretumor ecDNA accumulation in vivo in genetically engineered mouse neural stem cells. Variant and wild-type EGFR-ecD","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-07-15T05:52:06.133Z","creation":"2026-06-30T03:16:23.046Z"},"accession":"S-EPMC12498097","cross_references":{"pubmed":["40920091"],"doi":["10.1158/2159-8290.CD-24-1555"]}}