ArticleCancer discovery2025
Spatial-Temporal Diversity of Extrachromosomal DNA Shapes Urothelial Carcinoma Evolution and Tumor Immune Microenvironment.
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 19 papers.
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Who cites it
19 citing papers in PubMed.
- Article
- Multi-omics profiling of recurrence-associated extrachromosomal circular DNA characteristics and its prognostic potential in lung adenocarcinoma.Precision clinical medicine · 2026Article
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Aberrant p53 fuels macrophage immunoregulatory polarization and refractory clinical outcome in urothelial carcinoma.Journal for immunotherapy of cancer · 2026Article
- Targeting extrachromosomal DNA in human cancers.Nature reviews. Drug discovery · 2026Review
- Integrating single-cell and bulk transcriptomes to reveal prognostic and immunological features of ecDNA-related genes in osteosarcoma.Cancer immunology, immunotherapy : CII · 2026Article
- Review
- Accurate prediction of ecDNA in interphase cancer cells using deep neural networks.Communications biology · 2026Article
- The landscape and regulatory potential of eccDNAs in mammalian preimplantation embryos.Nature communications · 2026Article
- Extrachromosomal DNA and cancer: function, formation, and clinical implications.Journal of experimental & clinical cancer research : CR · 2026Review
- Loss of KDM6A-mediated genomic instability and metabolic reprogramming regulates response to therapeutic perturbations in bladder cancer.Nature communications · 2026Article
- Field cancerization in urothelial carcinoma: molecular alterations and clinical implications.Journal of Cancer · 2026Review
- Extrachromosomal DNA in Solid Tumors-Landscape, Immune Effects, and Resistance to Targeted Therapy.Oncology research · 2026Review
- ecPICK: A deep learning-enabled spatial diagnostic platform for direct ecDNA identification and clinical prognosis across pan-cancer histopathology.Theranostics · 2026Article
- Machine learning identified extrachromosomal DNA-related 12 gene signatures to predict cancer immunotherapy response.Cancer cell international · 2025Article
- ecDNA-driven oncogene super-expressors shape immunoevasive tumor microenvironment.bioRxiv : the preprint server for biology · 2025Article
- Clinical application of single-cell RNA sequencing in disease and therapy.Clinical and translational medicine · 2025Review
- Research Advances of Extrachromosomal Circular DNA in Breast Cancer.Cancer medicine · 2025Review
- The role of extrachromosomal DNA in tumorigenesis and progression.Frontiers in oncology · 2025Review
Corrections and comments
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Authors and funding
40 authors.
Funding
Abstract
Extrachromosomal DNA (ecDNA) presents a promising target for cancer therapy; however, its spatial–temporal diversity and influence on tumor evolution and the immune microenvironment remain largely unclear. We apply computational methods to analyze ecDNA from whole-genome sequencing data of 595 patients with urothelial carcinoma. We demonstrate that ecDNA drives clonal evolution through structural rearrangements during malignant transformation and recurrence of urothelial carcinoma. This supports a model wherein tumors evolve via the selective expansion of ecDNA-bearing cells. Through multiregional sampling of tumors, we demonstrate that ecDNA contributes to the evolution of multifocality and increased intratumoral heterogeneity. ecDNA is present in 36% of urothelial carcinoma tumors and correlates with an immunosuppressive phenotype and poor prognosis. Single-cell RNA sequencing analyses reveal that ecDNA+ malignant cells exhibit diminished expression of MHC class I molecules, enabling them to evade T-cell immunity. Finally, we show that sequencing of urinary sediment–derived DNA has excellent specificity in detecting ecDNA. Significance: Our comprehensive analysis of ecDNA in urothelial carcinoma reveals its crucial role in driving the evolution and heterogeneity of multifocal cancer, as well as its early involvement in tumorigenesis. Moreover, this study sheds light on immune evasion mechanisms associated with ecDNA and offers valuable insights for developing targeted therapeutic strategies.
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Registered trials
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