Evidence map›Paper›PMID 42665813›Full record

ArticleActa neuropathologica communications2026

Age-associated epigenomic heterogeneity in papillary tumors of the pineal region: a multicenter YoungNOA investigation.

Lazaros Lazaridis, Xiaomei Zhou, Raphael Bodensohn, Malte Mohme, Julia Onken, Regina von Manitius, Naomi Houedjissin, Tobias Blau, Ilinca Popp, Sarina Agkatsev and 40 more

Abstract readMulticenter Study
In one paragraph

Article in Acta neuropathologica communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

50 authors.

Lazaros Lazaridis *Department of Neurology, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany.
Xiaomei Zhou *Division of Clinical Neuro-Oncology, Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
Raphael BodensohnDepartment of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany.
Malte MohmeDepartment of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Julia OnkenDepartment of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Regina von ManitiusDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Naomi HouedjissinDepartment of Neurosurgery, Medical Faculty, Center of Neuro-Oncology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Tobias BlauInstitute of Neuropathology, University Medicine Essen, Essen, Germany.
Ilinca PoppDepartment of Radiation Oncology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Sarina AgkatsevDepartment of Neurology, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany.
Sabine SeidelDepartment of Neurology, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany.
Christina SchaubDepartment of Neurology, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany.
Maximilian ScheerDepartment of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.
Andre SagererDepartment of Neurosurgery, Universität Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Volker NeuschmeltingDepartment of General Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Davide TosinDepartment of Neurological Surgery, Ulm University Medical Center, Ulm, Germany.
Viktoria RufFaculty of Medicine, Center for Neuropathology and Prion Research, LMU Munich, Munich, Germany.
Michael C BurgerGoethe University, Dr. Senckenberg Institute of Neurooncology, Goethe University Hospital, Frankfurt Am Main, Germany.
Christoph OsterDivision of Clinical Neuro-Oncology, Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
Teresa SchmidtDivision of Clinical Neuro-Oncology, Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
Benjamin ThieleMedical Oncology, University Hospital Basel, Basel, Switzerland.
Jürgen HenchInstitute for Pathology and Medical Genetics, University Hospital Basel, Basel, Switzerland.
Stephan FrankInstitute for Pathology and Medical Genetics, University Hospital Basel, Basel, Switzerland.
Martin StuschkeDepartment of Radiotherapy, University Medicine Essen, University Duisburg-Essen, Essen, Germany.
Laurèl RauschenbachGerman Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, a Partnership Between DKFZ and University Hospital Essen, Germany, DKFZ-Division Translational Neuro-Oncology at the West German Cancer Center (WTZ), University Medicine Essen, University Duisburg-Essen, Essen, Germany.
Stephan TippeltDepartment of Pediatrics III, Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital of Essen, 45122, Essen, Germany.
Beate TimmermannDepartment of Particle Therapy, University Hospital Essen, West German Proton Therapy Centre Essen (WPE), West German Cancer Centre (WTZ), 45147, Essen, Germany.
Kathy KeyvaniInstitute of Neuropathology, University Medicine Essen, Essen, Germany.
Clemens SeidelDepartment of Radiotherapy and Radiation Oncology, University Hospital Leipzig, Leipzig, Germany.
Andrea TannapfelInstitute of Pathology, Ruhr University Bochum, Bochum, Germany.
Dorothea MillerDepartment of Neurosurgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany.
Niklas ThonDepartment of Neurosurgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany.
Joachim P SteinbachGoethe University, Dr. Senckenberg Institute of Neurooncology, Goethe University Hospital, Frankfurt Am Main, Germany.
Elke PfaffDepartment of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.
Georg Karpel-MasslerDepartment of Neurological Surgery, Ulm University Medical Center, Ulm, Germany.
Jörg FelsbergInstitute of Neuropathology, Medical Faculty, Heinrich-Heine-University Düsseldorf, and University Hospital Düsseldorf, Düsseldorf, Germany.
Guido ReifenbergerInstitute of Neuropathology, Medical Faculty, Heinrich-Heine-University Düsseldorf, and University Hospital Düsseldorf, Düsseldorf, Germany.
Marcos TatagibaDepartment of Neurosurgery, University Hospital Tübingen, Tübingen, Germany.
Ghazaleh TabatabaiDepartment of Neurology and Interdisciplinary Neuro-Oncology, University Hospital Tübingen, Hertie Institute for Clinical Brain Research, Center for Neuro-Oncology, Comprehensive Cancer Center, Eberhard-Karls-University Tübingen, Tübingen, Germany.
Jens SchittenhelmDepartment of Neuropathology, Institute of Pathology and Neuropathology, University Hospital Tübingen, Eberhard-Karls-University Tübingen, Tübingen, Germany.
Christian ThomasInstitute of Neuropathology, University Hospital Münster, Münster, Germany.
Martin HasselblattInstitute of Neuropathology, University Hospital Münster, Münster, Germany.
Corinna SeligerDepartment of Neurology, University Hospital Knappschaftskrankenhaus Bochum, Ruhr University Bochum, Bochum, Germany.
Christoph KleinschnitzDivision of Clinical Neuro-Oncology, Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.
Ulrich SureDepartment of Neurosurgery and Spine Surgery, University Medicine Essen, University Duisburg-Essen, Essen, Germany.
David CapperDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Michael PlattenDepartment of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neurosciences (MCTN), University of Heidelberg, Mannheim, Germany.
Felix BehlingDepartment of Neurosurgery, University Hospital Tübingen, Tübingen, Germany.
Michael MütherDepartment of Neurosurgery, University Hospital Münster, Münster, Germany.
Sied KebirDivision of Clinical Neuro-Oncology, Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. sied.kebir@uk-essen.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPapillary tumors of the pineal region (PTPR) are rare CNS neoplasms with adult and pediatric presentations, but whether age defines distinct molecular biology is unclear.

methodsWe assembled a multicenter retrospective cohort of 86 histologically confirmed PTPR with genome-wide DNA methylation data, comprising 62 adult and 24 pediatric tumors. Molecular subgroup, array platform, sex, and tumor purity were incorporated into multivariable models. Analyses included DNA methylation class assignment, differential methylation, copy-number variation (CNV), epigenetic mitotic-clock scores, methylation-based tumor microenvironment deconvolution, and descriptive survival evaluation.

resultsAdult and pediatric tumors mapped within the established PTPR-A and PTPR-B methylation framework rather than forming age-defined methylation classes. Pediatric tumors were enriched for PTPR-B (22 of 24 tumors [91.7%]) compared with adult tumors (39 of 62 [62.9%]). After adjustment for methylation-based subgroup as well as technical and biological covariates, 2,923 CpG probes were associated with age at a false discovery rate (FDR) threshold below 0.05, and 530 also met the prespecified effect-size threshold. Global methylation summaries were similar between age groups. CNV patterns were dominated by molecular subgroup; adjusted genomic CNV load was not independently associated with pediatric age. In contrast, epiTOC2 intrinsic rate score and the methylation signature represented by the first principal component (PC1) showed age-associated effects independent of molecular subgroup. Methylation-based deconvolution suggested a limited microenvironmental signal, with neutrophil fraction showing the most consistent adjusted association.

conclusionsAdult and pediatric PTPR share the established PTPR-A/PTPR-B framework. Pediatric tumors, particularly within PTPR-B, showed age-associated DNA methylation differences and higher epigenetic mitotic-clock (epiTOC2) scores in this retrospective cohort. These tissue-level associations do not establish clinical risk or treatment implications and require prospective clinical annotation and orthogonal validation.

Indexed as

Brain NeoplasmsCarcinoma, PapillaryPineal GlandPinealomaAdolescentAdultAgedAge FactorsChildChild, PreschoolDNA Copy Number VariationsDNA MethylationEpigenesis, GeneticEpigenomicsFemaleHumansDNA methylationEpigenomicPapillary tumors of the pineal region

Identifiers

PMID42665813
PMCPMC13525666

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