| Title: |
Methylated CfDNA may distinguish between high- and intermediate-risk uveal melanoma:a pilot study |
| Authors: |
Wu, Mike; de Bruyn, Daniël P.; Boers, Ruben G.; Beasley, Aaron B.; Hazelaar, Daan M.; Makrodimitris, Stavros; Boers, Joachim B.; Vaarwater, Jolanda; de Keizer, Ronald O.B.; Verdijk, Robert M.; Naus, Nicole C.; Paridaens, Dion; Wilting, Saskia M.; Gray, Elin S.; van IJcken, Wilfred F.J.; Gribnau, Joost; de Klein, Annelies; Brosens, Erwin; Kiliç, Emine |
| Source: |
Wu, M, de Bruyn, D P, the Rotterdam Ocular Melanoma Studygroup, Boers, R G, Beasley, A B, Hazelaar, D M, Makrodimitris, S, Boers, J B, Vaarwater, J, de Keizer, R O B, Verdijk, R M, Naus, N C, Paridaens, D, Wilting, S M, Gray, E S, van IJcken, W F J, Gribnau, J, de Klein, A, Brosens, E & Kiliç, E 2026, 'Methylated CfDNA may distinguish between high- and intermediate-risk uveal melanoma : a pilot study', Cancer Cell International, vol. 26, no. 1, 18. https://doi.org/10.1186/s12935-025-04093-2 |
| Publication Year: |
2026 |
| Subject Terms: |
/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being; name=SDG 3 - Good Health and Well-being |
| Description: |
Background: Uveal melanoma (UM) is a highly aggressive malignancy with a metastatic risk that depends on the molecular subclass. This subclass can be determined through molecular characterization of tumor-derived tissue. With eye-sparing treatments, tumor tissue is rarely available for molecular testing. We hypothesized that minimal invasive biomarkers such as methylated cell-free DNA (cfDNA) or circulating tumor DNA (ctDNA) can be used for prognosis and monitoring of patients. Methods: Plasma cfDNA was isolated from healthy blood donors (HBDs, N = 19) and UM patients (N = 22). Plasma was collected at baseline (localized disease, N = 13) and during follow-up (metastatic disease, N = 9) from independent patients with high metastatic risk (HR, N = 11) (monosomy 3 and/or BAP1-mutated tumor) or intermediate metastatic risk (IR, N = 11) (disomy 3 and/or SF3B1-mutated tumor). Methylation signatures were determined using genome-wide LpnPI-based methylated DNA sequencing (MeD-seq). Samples with a CpG/reads ratio < 20% (N = 3) were excluded. IchorCNA was used to estimate the tumor fraction. cfDNA samples with detectable tumor fraction (N = 2) were analyzed separately from the other cfDNA samples without detectable tumor fraction (N = 18) to reduce noise in downstream analyses. Differentially methylated regions (DMRs) were identified between the following predefined subgroups: UM (N = 11) vs. HBDs (N = 19), and HR (N = 10) vs. IR (N = 7). To visualize clustering, principal component analysis (PCA) and hierarchical clustering was performed on the DMRs with fold change > 2.0. Gene set enrichment analysis (GSEA, Z-score > 2.0 and p < 0.05) was performed to evaluate biological relevance. Results: Distinct clustering was observed between UM and HBDs samples, and between HR and IR samples, although outliers were present in the latter comparison. GSEA implicated eight canonical pathways including the S100 Family Signaling Pathway and RAF/MAP kinase cascade, which are linked to tumorigenesis and immune processes. ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
1475-2867 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41382221; info:eu-repo/semantics/altIdentifier/pissn/1475-2867; info:eu-repo/semantics/altIdentifier/eissn/1475-2867 |
| DOI: |
10.1186/s12935-025-04093-2 |
| Availability: |
https://pure.eur.nl/en/publications/f9af7b9e-95e4-4d9d-870f-a602bfebb27d; https://doi.org/10.1186/s12935-025-04093-2; https://pure.eur.nl/ws/files/223072755/Methylated_CfDNA_may_distinguish_between_high-_and_intermediate-risk_uveal_melanoma.pdf; https://www.scopus.com/pages/publications/105027792443 |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.BADB0C58 |
| Database: |
BASE |