ArticleCommunications medicine2026
Identification and validation of liquid biopsy-based methylation biomarkers for germ cell tumor subtypes.
Article in Communications medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Identification and validation of liquid biopsy-based methylation biomarkers for germ cell tumor subtypes.Communications medicine · 2026Article
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Authors and funding
8 authors.
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Abstract
backgroundHuman germ cell tumors (GCTs) occur in infants, children, and adults, and present as germinomatous and/or non-germinomatous (embryonal carcinoma (EC), teratoma, yolk sac tumor (YST), and choriocarcinoma) histologies at gonadal or extragonadal locations. Accurate subtyping is crucial for prognosis and treatment, but current clinical biomarkers lack sensitivity and specificity (serum proteins), or require a tissue biopsy (for histological and immunohistochemical characterization). Hence, less-invasive and improved subtype-specific biomarkers have significant potential for clinical utility.
methodsWe conducted an integrated DNA methylation analysis (450K/EPIC array) from 16 (three original and 13 published) datasets, including 719 GCTs, 109 healthy testis, and 221 healthy peripheral blood samples. Unsupervised hierarchical clustering, UMAP, and Heidelberg Central Nervous System tumor methylation classification were implemented for GCT global methylation profiling, followed by differential methylation analysis for in silico GCT subtype-specific biomarker identification, and methylation-sensitive restriction enzyme-based qPCR for in vitro and in vivo biomarker validation.
resultsWe demonstrate that GCTs contain unique methylation profiles based on their histology, regardless of tumor location and the patient's age or sex. Per GCT histology, we identify numerous differentially methylated regions as potential biomarkers. As proof of concept, two YST-specific (APC and DPP7) and two EC-specific (GATA4 and FBRS) biomarkers are validated in tumor DNA, of which DPP7 is also detectable in GCT serum-derived cell-free DNA.
conclusionsWe present a method for in silico identification and subsequent in vitro and in vivo validation of GCT subtype-specific methylation-derived liquid biopsy-based biomarkers with potential to complement the limitations of current biomarkers. Our bioinformatic pipeline is easily transferrable encouraging additional applications in pan(pediatric)-cancer studies beyond GCTs.
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