Cell-free DNA methylome and fragmentome analysis for disease relapse monitoring in patients with Ewing Sarcoma
Open accessAbstract
Summary: Liquid biopsies and cell-free DNA (cfDNA) offer minimally invasive methods for the diagnosis and monitoring of Ewing Sarcoma (EwS). EwS have a low tumour mutational burden and their detection with plasma cfDNA is challenging. We hypothesised that analysing the cfDNA methylome and fragmentome could enhance sensitivity for detecting EwS and identifying early disease recurrence. We conducted whole-genome and methylome sequencing of cfDNA from 68 serial samples of 15 patients with EwS and 3 patients with CIC-rearranged sarcoma (CIC). With EwingSign, a new machine learning model, we identified EwS or CIC in a test set for 10 out of 12 patients at diagnosis and 15 out of 18 clinically confirmed relapse events. 0 out of 29 non-cancer controls were detected positive with EwingSign. These findings indicate that cfDNA methylome and fragmentome analysis, if validated in a larger cohort, could improve disease detection, monitoring and relapse identification in patients with EwS.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Pediatric sarcomas are a biologically heterogeneous group of aggressive solid tumors with a persistently high risk of relapse and metastatic progression.
“Among childhood malignancies, pediatric sarcomas including Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma represent a biologically heterogeneous group of aggressive solid tumors with a persistently high risk of relapse and metastatic progression [2,3,4,5].”
Cites
Grünewald, T. G. P., Cidre-Aranaz, F., Surdez, D., Tomazou, E. M., de Álava, E., Kovar, H., Sorensen, P. H., Delattre, O., & Dirksen, U. (2018) · Nature Reviews Disease Primers · doi:10.1038/s41572-018-0003-x · Cited by 873 · see citing works
Peneder, P., Stütz, A. M., Surdez, D., Krumbholz, M., Semper, S., Chicard, M., Sheffield, N. C., Pierron, G., Lapouble, E., Tötzl, M., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23445-w · Cited by 200 · see citing works
Self-citationShulman, D. S., Klega, K., Imamovic-Tuco, A., Clapp, A., Nag, A., Thorner, A. R., Van Allen, E., Ha, G., Lessnick, S. L., Gorlick, R., et al. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0212-9 · Cited by 149 · see citing works
Shukla, N. N., Patel, J. A., Magnan, H., Zehir, A., You, D., Tang, J., Meng, F., Samoila, A., Slotkin, E. K., Ambati, S. R., et al. (2017) · JCO Precision Oncology · doi:10.1200/po.16.00028 · Cited by 52 · see citing works
A comprehensive overview of liquid biopsy applications in pediatric solid tumors
Janssen, F. W., Lak, N. S. M., Janda, C. Y., Kester, L. A., Meister, M. T., Merks, J. H. M., van den Heuvel-Eibrink, M. M., van Noesel, M. M., Zsiros, J., Tytgat, G. A. M., et al. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00657-z · Cited by 32 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kurdi, M., Hassan, A., Reda, B., Nooh, A., Alsobaie, M., Alkhotani, A., Mirdad, D. S., Almansouri, M., Khashoggi, K., Halwani, M., et al. (2026) · Oncology Research · doi:10.32604/or.2026.078833 · Cited by 2 · see citing works
“Among childhood malignancies, pediatric sarcomas including Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma represent a biologically heterogeneous group of aggressive solid tumors with a persistently high risk of relapse and metastatic progression [2–5].”
- Authors
- Richardson, S. A., Gulati, G., Harker, P. J. B., Redfern, A., Pearce, S. P., Karimpour, M., Hill, S. M., Makeev, V. J., Brennan, B., Lee, A. T., Clipson, A., Dive, C., Rothwell, D. G., McCabe, M. G., & Mouliere, F.
- Affiliations
- Cancer Research UK (GB)
- Royal Manchester Children's Hospital (GB)
- The Christie NHS Foundation Trust (GB)
- Corresponding author
- Richardson, Sophie A.
- ORCID
- Venue
- medRxiv
- Publisher
- openRxiv
- Published
- 2025-04-28
- OpenAlex
- W4409880005
- Cited by
- 0
- References
- 5
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- medRxiv (acceptedVersion, cc-by-nc-nd)
- Funders
- Children's Cancer Research Fund
- Cancer Research UK (A27412, C5759, C5759/A27412, 100001)
- National Institute for Health and Care Research (NIHR 203308, C5759)
- Manchester Biomedical Research Centre (NIHR 203308)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Keywords
- Ewing sarcoma, cell-free DNA, DNA methylation, liquid biopsy, CIC-rearranged sarcoma, machine learning classifiers, cancer detection
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
