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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Adult 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Adult 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40478-026-02411-x","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:45:00Z","timestamp":1787928300000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age-associated epigenomic heterogeneity in papillary tumors of the pineal region: a multicenter YoungNOA 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Curr Oncol 28:1274\u20131279. https:\/\/doi.org\/10.3390\/curroncol28020121","journal-title":"Curr Oncol"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40478-026-02411-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-026-02411-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-026-02411-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:55:58Z","timestamp":1787928958000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40478-026-02411-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2411"],"URL":"https:\/\/doi.org\/10.1186\/s40478-026-02411-x","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]},"assertion":[{"value":"2 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study protocol was approved by the lead Ethics Committee of the University Hospital Essen, approval number 20-9431-BO, and by the institutional review boards of all participating centers. Written informed consent was obtained from living patients; for deceased patients or when re-consent was impracticable, consent was waived in accordance with national regulations and ethics committee approval.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Lazaros Lazaridis received honoraria and travel support from Novocure. Raphael Bodensohn received honoraria from Novocure, Brainlab and Pierre-Fabre. Christoph Oster received travel support from Novocure and honoraria from Horizon and Novocure. He received a Clinician Scientist fellowship of the University Medicine Essen Clinician Scientist Academy (UMEA) sponsored by the faculty of medicine and Deutsche Forschungsgemeinschaft (DFG) and a research grant from Servier. Corinna Seliger received honoraria and\/or travel support from Medac, Servier, Orphalan, and Novocure. Michael Platten received research grants from Bayer, Roche, Pfizer, Merck; he received consulting fees from Servier (institutional), and honoraria from Roche (institutional). Sied Kebir is a fellow of the Else Kr\u00f6ner-Fresenius Foundation and the Advanced Clinician Scientist Program (UMEA\n                      2\n                      ), funded by the Federal Ministry of Research, Technology and Space (BMFTR) in the framework of the Advanced Clinician Scientist Programme UMEA\n                      2\n                      ; 01EO210. He received research grants from Novocure and Servier, as well as honoraria and consulting fees from Novocure (institutional). Felix Behling received travel support from Medac and Servier. All remaining authors have declared no conflicts of interest.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"180"}}