ArticleCancer discovery2025
Extrachromosomal DNA-Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma.
Article in Cancer discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Receptor tyrosine kinase targeted therapies in glioblastoma: a systematic review.Frontiers in medicine · 2026Pooled it
- Interpretable prototype learning for EGFR amplification prediction from whole-slide images in glioblastoma.Journal of pathology informatics · 2026Article
- Spatial chromatin architecture and accessibility co-profiling of mammalian tissues.Nature methods · 2026Article
- Extrachromosomal DNA as a platform for epigenetic reprogramming in cancer.Molecular cancer · 2026Review
- The shared evolutionary capacities of plasmids and extrachromosomal DNA.Nature reviews. Genetics · 2026Review
- Extrachromosomal DNA in urothelial carcinoma: mechanisms and clinical applications.Nature reviews. Urology · 2026Review
- Exploring the landscape of targetable alterations in patients with glioblastoma.Nature reviews. Clinical oncology · 2026Review
- scAmp enables focal gene amplification analysis from single-cell data.Nature communications · 2026Article
- Article
- Beyond chromosomes: exploring the diverse functions of extrachromosomal circular DNA.Journal of advanced research · 2026Review
- Organoid technology in cancer research.Molecular biomedicine · 2026Review
- Murine osteosarcoma recapitulates the driver landscape and genomic complexity of osteosarcoma evolution in humans.bioRxiv : the preprint server for biology · 2026Article
- Applications of transcranial focused ultrasound for primary brain tumors.Neuro-oncology advances · 2026Review
- Beyond Darwin: reactive heredity, burst-drift dynamics and eco‑evolutionary control of cancer.Molecular cancer · 2026Review
- An EGFR co-amplified lncRNA HELDR promotes glioblastoma malignancy through KAT7-driven gene programs.Nature cell biology · 2026Article
- lncRNA in EGFR‑driven glioblastoma.Nature cell biology · 2026Article
- Chromosome-arm-specific telomere length governs dual modes of structural genome evolution in IDH-mutant astrocytoma.bioRxiv : the preprint server for biology · 2026Article
- Review
- Fast and accurate resolution of ecDNA sequence using Cycle-Extractor.bioRxiv : the preprint server for biology · 2026Article
- Accurate prediction of ecDNA in interphase cancer cells using deep neural networks.Communications biology · 2026Article
Corrections and comments
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Authors and funding
35 authors.
Funding
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-ecDNAs often coexist in GBM. Those variant EGFR-ecDNAs, most commonly EGFRvIII-ecDNA, always derive from preexisting wild-type EGFR-ecDNAs, occur early, and reach high abundance. Our results suggest that the ecDNA oncogenic makeup determines unique evolutionary trajectories. New concepts such as ecDNA clonality and heteroplasmy require a refined evolutionary interpretation of genomic data in a large subset of GBMs. SIGNIFICANCE: We study spatial patterns of ecDNA-amplified oncogenes and their evolutionary properties in human GBM, revealing an ecDNA landscape and ecDNA oncogene-specific evolutionary histories. ecDNA accumulation can precede clonal expansion, facilitating the emergence of EGFR oncogenic variants, reframing our interpretation of genomic data in a large subset of GBMs. See related commentary by Korsah et al., p. 1979.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.