EPCO-28. THE MOLECULAR LANDSCAPE AND ITS PROGNOSTIC IMPLICATIONS IN ADULT PAPILLARY TUMORS OF THE PINEAL REGION - A MULTICENTER YOUNGNOA INVESTIGATION
Abstract Papillary tumors of the pineal region (PTPR) are rare central nervous system (CNS) neoplasms with variable clinical behavior, where robust prognostic biomarkers for adult patients remain elusive. Here, we performed comprehensive DNA methylation and copy number variation (CNV) analyses on 64 adult PTPRs from newly assembled (n=21) and public (n=43) cohorts to validate molecular subtypes and refine prognostic stratification. We confirmed distinct PTPR-A and PTPR-B molecular profiles, with PTPR-B showing a non-significant trend towards poorer progression-free survival (PFS) in adult-specific analyses. Exploratory comparisons between Favorable (PFS > 50 months) and Unfavorable (PFS < 50 months) Prognosis Groups consistently revealed hypermethylation of G protein-coupled receptor (GPCR) signaling pathway gene promoters in Unfavorable PTPR across independent cohorts. Unfavorable cases also showed preliminary evidence of accelerated epigenetic aging (epiTOC2/3). Integrative Unsupervised Uniform Manifold Approximation and Projection (UMAP) analysis positioned PTPR-B near WNT-medulloblastoma. Our findings delineate the adult PTPR molecular landscape, suggest novel prognostic avenues beyond the A/B classification implicating GPCR signaling and epigenetic deregulation, and underscore the critical need for larger collaborative studies to develop targeted therapies for this rare tumor.
Authors
- Martin Glas (ORCID: https://orcid.org/0000-0003-3167-3403)
- Corinna Seliger (ORCID: https://orcid.org/0000-0002-4923-4495)
- Christoph Kleinschnitz (ORCID: https://orcid.org/0000-0002-1650-8875)
- Raphael Bodensohn (ORCID: https://orcid.org/0000-0002-1114-2771)
- Christian Johannes Hartmann (ORCID: https://orcid.org/0009-0004-3700-3536)
- Guido Reifenberger (ORCID: https://orcid.org/0000-0002-1419-9837)
- Clemens Seidel (ORCID: https://orcid.org/0000-0001-8178-5089)
- Michael C. Burger (ORCID: https://orcid.org/0000-0002-6927-0987)
- Regina von Manitius
- Christian Thomas (ORCID: https://orcid.org/0000-0002-6642-7774)
- Volker Neuschmelting (ORCID: https://orcid.org/0000-0001-7527-6990)
- Tobias Blau (ORCID: https://orcid.org/0000-0003-0439-971X)
- Sied Kebir (ORCID: https://orcid.org/0000-0002-0678-5852)
- Felix Behling (ORCID: https://orcid.org/0000-0002-1083-1276)
- Katharina J. Wenger (ORCID: https://orcid.org/0000-0002-8640-6858)
- André Sagerer
- David Capper (ORCID: https://orcid.org/0000-0003-1945-497X)
- Jens Schittenhelm (ORCID: https://orcid.org/0000-0002-9168-6209)
- Stefan M. Pfister (ORCID: https://orcid.org/0000-0002-5447-5322)
- Lazaros Lazaridis (ORCID: https://orcid.org/0000-0002-9538-4566)
- Benjamin Thiele (ORCID: https://orcid.org/0000-0002-4096-3309)
- Davide Tosin
- Kathy Keyvani (ORCID: https://orcid.org/0000-0003-2558-5159)
- Teresa Schmidt (ORCID: https://orcid.org/0000-0003-2434-8223)
- Ulrich Sure (ORCID: https://orcid.org/0000-0002-9073-1821)
- Ilinca Popp (ORCID: https://orcid.org/0000-0001-6702-3619)
- Kenneth Aldape (ORCID: https://orcid.org/0000-0001-5119-7550)
- Andrea Tannapfel (ORCID: https://orcid.org/0000-0002-0711-7100)
- Malte Mohme (ORCID: https://orcid.org/0000-0003-0627-9092)
- Michael Müther (ORCID: https://orcid.org/0000-0001-9427-5555)
- Michael Platten (ORCID: https://orcid.org/0000-0002-4746-887X)
- Stephan Frank (ORCID: https://orcid.org/0000-0001-6165-0187)
- Jörg Steinbach (ORCID: https://orcid.org/0000-0002-1708-6440)
- Julia Onken (ORCID: https://orcid.org/0000-0002-2859-4395)
- Martin Stuschke (ORCID: https://orcid.org/0000-0001-6836-0940)
- Viktoria Ruf
- Christoph Oster (ORCID: https://orcid.org/0000-0002-0683-0430)
- Niklas Thon (ORCID: https://orcid.org/0000-0003-0011-5281)
- Elke Pfaff (ORCID: https://orcid.org/0000-0002-3967-2264)
- Jörg Felsberg
- Georg Karpel‐Massler (ORCID: https://orcid.org/0000-0001-8236-5369)
- Sarina Agkatsev
- Sabine Seidel (ORCID: https://orcid.org/0000-0002-1671-3297)
- Jürgen Hench
- Martin Hasselblatt
- Maximilian Scheer
- Naomi Houedjissin
Institutions
- Goethe University Frankfurt (DE)
- Goethe-Institute United Kingdom (GB)
- Universität Hamburg (DE)
- University of Mannheim (DE)
- University of Cologne (DE)
- Universität Ulm (DE)
- Heidelberg University (DE)
- University Medical Center Freiburg (DE)
- University Hospital Heidelberg (DE)
- University Hospital of Basel (CH)
- LMU Klinikum (DE)
- Medizinische Hochschule Hannover (DE)
- University Hospital Münster (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Bernstein Center for Computational Neuroscience Heidelberg-Mannheim (DE)
- Universitätsklinikum Knappschaftskrankenhaus Bochum (DE)
- Essen University Hospital (DE)
- University Children's Hospital Tübingen (DE)
- University Hospital Leipzig (DE)
- University Hospital Frankfurt (DE)
- National Cancer Institute (US)
- Center for Cancer Research (US)
- University Hospital in Halle (DE)
- University Hospital Cologne (DE)
- University Hospital Ulm (DE)
- University Medical Centre Mannheim (DE)
- University Hospital Carl Gustav Carus (DE)
- Heinrich Heine University Düsseldorf (DE)
- University of Duisburg-Essen (DE)
- Charité - Universitätsmedizin Berlin (DE)
- University of Tübingen (DE)
- Ludwig-Maximilians-Universität München (DE)
- Ruhr University Bochum (DE)
Publication Details
- Journal
- Neuro-Oncology
- Published
- 2025-11-01
- DOI
- https://doi.org/10.1093/neuonc/noaf201.0028
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00