Evidence map›Paper›PMID 41998312›Full record

ArticleCommunications medicine2026

Identification and validation of liquid biopsy-based methylation biomarkers for germ cell tumor subtypes.

Ferdinand W Janssen, Ad J M Gillis, Puck B Gouswaart, Lennart A Kester, Hirokazu Takami, Koichi Ichimura, Thomas F Eleveld, Leendert H J Looijenga

Abstract read
In one paragraph

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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0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Ferdinand W JanssenPrincess Máxima Center, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0003-3144-3376
Ad J M GillisPrincess Máxima Center, Utrecht, The Netherlands.
Puck B GouswaartPrincess Máxima Center, Utrecht, The Netherlands.ORCID http://orcid.org/0009-0002-8136-4289
Lennart A KesterPrincess Máxima Center, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-8259-9971
Hirokazu TakamiDepartment of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
Koichi IchimuraDepartment of Pathology, Kyorin University Faculty of Medicine, Tokyo, Japan.
Thomas F EleveldPrincess Máxima Center, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0001-8580-4822
Leendert H J LooijengaPrincess Máxima Center, Utrecht, The Netherlands. L.Looijenga@prinsesmaximacentrum.nl.ORCID http://orcid.org/0000-0002-8146-1911

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Identifiers

PMID41998312
PMCPMC13275915

What Socratic holds

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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 Socratic graph.