ArticleNature genetics2026
A microenvironment-determined risk continuum refines subtyping in meningioma and reveals determinants of machine learning-based tumor classification.
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Article in Nature genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8citing papers in PubMed
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Who cites it
8 citing papers in PubMed.
- Immune-Enriched Versus Matrix-Remodeling Microenvironments in Psammoma Body-Rich and Psammoma Body-Poor WHO Grade I Meningiomas: An Exploratory Transcriptomic Study.Neuropathology : official journal of the Japanese Society of Neuropathology · 2026Article
- Modeling meningioma in vitro in the omics era.Human cell · 2026Review
- DNA methylation profiling identifies long-range epigenetic silencing of clustered protocadherins as a key determinant of meningioma progression.Nature communications · 2026Article
- Distinct molecular subgroups in pediatric and young-onset meningiomas require age-adapted risk stratification.Nature communications · 2026Article
- Synthetic MRI and Delta Histogram Analysis: A Step Forward in Noninvasive Meningioma Grading.Radiology. Imaging cancer · 2026Article
- Risk stratification for meningiomas with discordant molecular classification.Acta neuropathologica · 2026Article
- A proteogenomic RNA processing mechanism drives sex differences in meningioma.Research square · 2026Article
- Loss of meningothelial identity and mesenchymal fate switching in NF2-mutant meningiomas.Acta neuropathologica · 2026Article
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Authors and funding
69 authors.
Sybren L N Maas *Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. S.L.N.Maas@lumc.nl.ORCID http://orcid.org/0000-0002-8745-4405
Yiheng Tang *Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-9484-3353
Eric Stutheit-Zhao *Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada.
Ramin Rahmanzade *Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
Christina BlumeDepartment of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-1438-9304
Thomas HielscherDepartment of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Ferdinand ZettlDepartment of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-2802-3813
Salvatore BenfattoDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4439-3136
Domenico CalafatoDivision of AI in Oncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-9636-9819
Martin SillHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0001-7616-7665
Jasim Kada BenotmaneTranslational Neurosurgery, Neurosurgical Clinic, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Yahaya A YaboTranslational Neurosurgery, Neurosurgical Clinic, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.ORCID http://orcid.org/0000-0002-1128-6038
Felix BehlingDepartment of Neurosurgery, University Hospital Augsburg, Augsburg, Germany.
Abigail SuwalaDepartment of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
Helin KardoDepartment of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-7396-9160
Michael RitterDepartment of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
Matthieu PeyreSorbonne Université - Department of Neurosurgery, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris, France.ORCID http://orcid.org/0000-0001-8470-9516
Roman SankowskiInstitute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0001-9215-8021
Konstantin OkonechnikovHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Philipp SieversDepartment of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-3237-6021
Areeba PatelDepartment of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
David ReussDepartment of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
Mirco J FriedrichGerman Cancer Research Center (DKFZ), JRG Hematology and Immune Engineering, Heidelberg, Germany.
Damian StichelDepartment of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
Daniel SchrimpfDepartment of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.
Thierry P P Van den BoschDepartment of Pathology, Brain Tumor Center, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Katja BeckGerman Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany.
Hans-Georg WirschingDepartment of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
Gerhard JungwirthDepartment of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.
C Oliver HanemannFaculty of Health, Peninsula Medical School, University of Plymouth, Plymouth, UK.ORCID http://orcid.org/0000-0002-1951-1025
Katrin LamszusDepartment of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Nima EtminanDepartment of Neurosurgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Andreas UnterbergDepartment of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.
Christian MawrinDepartment of Neuropathology, University Hospital Magdeburg, Magdeburg, Germany.ORCID http://orcid.org/0000-0002-6677-3124
Marc RemkeDepartment of Pediatric Hematology and Oncology, University Medical Center of Saarland, Saarland University, Homburg/Saar, Germany.
Olivier AyraultInstitut Curie, PSL Research University, INSERM U1330/CNRS EMR 8001. Children's Oncology Research Unit (CONCERT), Paris, France.ORCID http://orcid.org/0000-0002-7942-6674
Peter LichterDivision of Molecular Genetics, German Cancer Research Center (DKFZ), and NCT Heidelberg, Heidelberg, Germany.
Guido ReifenbergerInstitute of Neuropathology, Heinrich Heine University, Medical Faculty, and University Hospital Düsseldorf, Düsseldorf, Germany.
Michael PlattenGerman Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-4746-887X
Tim KacprowskiChair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, Freising, Germany.ORCID http://orcid.org/0000-0002-5393-2413
Markus ListChair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, Freising, Germany.ORCID http://orcid.org/0000-0002-0941-4168
Josch K PaulingLipiTUM, Chair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, Freising, Germany.
Jan BaumbachChair of Experimental Bioinformatics, TUM School of Life Sciences, Technical University of Munich, Freising, Germany.ORCID http://orcid.org/0000-0002-0282-0462
Till MildeHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-7267-1052
Rachel GrossmannDepartment of Neurosurgery, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Zvi RamDepartment of Neurosurgery, Tel Aviv Medical Center, Tel Aviv, Israel, and School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Miriam RatliffDepartment of Neurosurgery, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.ORCID http://orcid.org/0000-0002-9464-6544
Jan-Philipp MallmSingle-cell Open Lab, German Cancer Research Centre (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-7059-4030
Marian C NeidertDepartment of Neurosurgery and Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
Eelke M BosDepartment of Neurosurgery, Brain Tumor Center, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0003-3647-6740
Marco PrinzInstitute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-0349-1955
Michael WellerDepartment of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-1748-174X
Till AckerInstitute of Neuropathology, Justus-Liebig-University Gießen, Giessen, Germany.
Felix J HartmannGerman Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-4174-2276
Matthias PreusserDivision of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0000-0003-3541-2315
Ghazaleh TabatabaiDepartment of Neurology, University Hospital Tübingen, Eberhard-Karls-University Tübingen, Tübingen, Germany.
Christel Herold-MendeDepartment of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-1915-745X
Sandro M KriegDepartment of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-4050-1531
David T W JonesHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-2036-5141
Stefan M PfisterHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-5447-5322
Wolfgang WickDepartment of Neurology and Neurooncology Program, National Center for Tumor Diseases, Heidelberg University & German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-6171-634X
Michel KalamaridesSorbonne Université - Department of Neurosurgery, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris, France.
Andreas von DeimlingDepartment of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-5863-540X
Dieter Henrik HeilandTranslational Neurosurgery, Neurosurgical Clinic, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.ORCID http://orcid.org/0000-0002-9258-3033
Volker HovestadtDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3480-6649
Moritz GerstungDivision of AI in Oncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0001-6709-963X
Matthias SchlesnerBiomedical Informatics, Data Mining and Data Analytics, Faculty of Applied Computer Science and Medical Faculty, University of Augsburg, Augsburg, Germany.ORCID http://orcid.org/0000-0002-5896-4086
German “Aggressive Meningiomas” Consortium (KAM)
Felix SahmDepartment of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany. Felix.Sahm@med.uni-heidelberg.de.ORCID http://orcid.org/0000-0001-5441-1962
Funding
No grant is acknowledged in the PubMed record.
Abstract
Classification of tumors in neuro-oncology today relies on molecular patterns (mostly DNA methylation) and their machine learning-supported interpretation. Understanding the process of algorithmic interpretation is essential for safe application in clinical routine. This is paradigmatically true for the most common primary intracranial tumor in adults, meningioma. Here, by applying multiomic profiling and multiple lines of orthogonal computational evaluation in multiple independent datasets, we found that not only tumor cell characteristics but also incremental changes in the tumor microenvironment (TME) have impact on epigenetic meningioma classification and clinical outcome. Besides revealing the decisive role of non-neoplastic cells in the CNS methylation classifier, this challenges the model of distinct meningioma subgroups toward a TME-determined risk continuum. This refines current controversies in molecular meningioma subtyping. In addition, we apply these learnings to devise and validate a simple diagnostic approach for increased clinical prediction accuracy based on immunohistochemistry, which is also applicable in resource-limited settings.
Indexed as
Machine LearningMeningeal NeoplasmsMeningiomaTumor MicroenvironmentClassification AlgorithmsDNA MethylationGene Expression ProfilingHumans
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