ArticleNature medicine2017
DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
158 citing papers in PubMed, 1 synthesis or guideline pooled it, 257 citations in OpenAlex.
- Biological Sample Collection to Advance Research and Treatment: A Fight Osteosarcoma Through European Research and Euro Ewing Consortium Statement.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Guideline
- Open-Label, Multicenter, Phase I/II, First-in-Human Trial of TK216: A First-Generation EWS::FLI1 Fusion Protein Antagonist in Ewing Sarcoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- A Practical Compass to Biological Digital Resources and Omics Integration in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Chromatin Immunoprecipitation Followed by Next-Generation Sequencing in Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- The ITCC-P4 PDX Platform Enables Preclinical Testing of Pediatric Cancers.Cancer research · 2026Article
- SNHG family lncRNAs promote Ewing sarcoma cell fitness through intronic snoRNA-guided rRNA modifications.NAR cancer · 2026Article
- What's new in pediatric bone sarcomas and benign bone tumors.Journal of children's orthopaedics · 2026Article
- Article
- Low Depth Epigenetic Mapping of Maturation Versus Retrodifferentiation in HepaRG Cells.Epigenomes · 2026Article
- DNA methylation heterogeneity in complex tumor microenvironment: Quantitative methods, influencing factors, and clinical implications.Genes & diseases · 2026Review
- Potential biomarkers of Ewing sarcoma identified through a Europe-wide analysis of prospectively collected samples.Scientific reports · 2026Article
- Cell-free DNA methylome and fragmentome analysis for relapse monitoring of Ewing sarcoma.EMBO molecular medicine · 2026Article
- Proteomic landscape of Ewing sarcoma primary tumors and metastases.Nature communications · 2026Article
- LSD1 Performs Demethylase-Independent and Context-Specific Roles in Ewing Sarcoma.Cancer research communications · 2026Article
- Article
- New cell lines expanding the diversity of Ewing sarcoma models.International journal of cancer · 2026Article
- Fusion oncoproteins orchestrate tumorigenesis and sustain malignant progression via a positive feedback mechanism.Cell & bioscience · 2026Review
- The hegemonic EWSR1::ETS oncoprotein overrules core regulatory circuitry principles in Ewing sarcoma.NPJ precision oncology · 2025Article
- LSD1 Performs Demethylase-Independent and Context-Specific Roles in Ewing Sarcoma.bioRxiv : the preprint server for biology · 2025Article
- New Approaches to Investigate Novel Agents in Ewing Sarcoma: A Report From the Children's Oncology Group Bone Tumor Committee.Pediatric blood & cancer · 2025Review
98 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
38 authors at 12 institutions in 4 countries.
Funding
Abstract
Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genetically homogeneous cancers. We performed genome-scale DNA methylation sequencing for a large cohort of Ewing sarcoma tumors and analyzed epigenetic heterogeneity on three levels: between cancers, between tumors, and within tumors. We observed consistent DNA hypomethylation at enhancers regulated by the disease-defining EWS-FLI1 fusion protein, thus establishing epigenomic enhancer reprogramming as a ubiquitous and characteristic feature of Ewing sarcoma. DNA methylation differences between tumors identified a continuous disease spectrum underlying Ewing sarcoma, which reflected the strength of an EWS-FLI1 regulatory signature and a continuum between mesenchymal and stem cell signatures. There was substantial epigenetic heterogeneity within tumors, particularly in patients with metastatic disease. In summary, our study provides a comprehensive assessment of epigenetic heterogeneity in Ewing sarcoma and thereby highlights the importance of considering nongenetic aspects of tumor heterogeneity in the context of cancer biology and personalized medicine.
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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.