ArticleNature medicine2023
Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology.
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Article in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 94 papers.
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94citing papers in PubMed
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Who cites it
94 citing papers in PubMed.
- "Updates on diagnostic and prognostic molecular biomarkers of CNS tumors".Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Spatial Omics in High-Grade Gliomas: Mapping Immune-Tumor Niches for Precision Therapy.Cancer medicine · 2026Review
- Neuro-immune crosstalk in lung cancer brain metastasis: mechanisms, therapeutic targets, and translational opportunities.Medical oncology (Northwood, London, England) · 2026Review
- Overactivation of SHH signaling induces a cascade of dedifferentiation and oncogenesis in a new mouse model for choroid plexus carcinoma.Acta neuropathologica communications · 2026Article
- Distinct molecular subgroups in pediatric and young-onset meningiomas require age-adapted risk stratification.Nature communications · 2026Article
- Extracellular Vesicles in the Biology and Liquid Biopsy Diagnostics of Pediatric High-Grade Glioma - Emerging Findings and Opportunities.Journal of extracellular biology · 2026Review
- Hetairos is a histology-based artificial intelligence model for predicting central nervous system tumor methylation subtypes.Nature cancer · 2026Article
- Molecular regulators of thromboinflammation and angiogenesis in pediatric cancer: emerging roles of noncoding RNAs, epigenetics, and extracellular vesicles - narrative review.Annals of medicine and surgery (2012) · 2026Review
- Identification and validation of liquid biopsy-based methylation biomarkers for germ cell tumor subtypes.Communications medicine · 2026Article
- Molecular and clinical stratification of astroblastomas: Three distinct fusion-defined groups informing risk-adapted treatment strategies.Neuro-oncology · 2026Article
- Prognostic Importance of Histomolecular Subtyping of Central Nervous System Gliomas in Low and Middle-Income Countries.Brain tumor research and treatment · 2026Article
- M-PACT leverages cell-free DNA methylomes to achieve robust classification of pediatric brain tumors.Nature cancer · 2026Article
- Impact of Circulating Tumor DNA and Copy-Number Alterations on Clinical Outcome in Relapsed/Refractory Germ Cell Tumors Treated With Salvage High-Dose Chemotherapy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Article
- Single-cell and multi-omics analysis identifies mitophagy-related biomarkers and therapeutic targets in ischemic stroke.Scientific reports · 2026Article
- Integrative Multiomics and Drug Sensitivity Profiling Reveal Potential Biomarkers and Therapeutic Strategies in Pediatric Solid Tumors.Cancer research · 2026Article
- Developing an advanced risk stratification model for pediatric intracranial ependymoma based on the prospective trial E-HIT2000 and subsequent registries.Neuro-oncology · 2026Article
- Investigation of a global mouse methylome atlas reveals subtype-specific copy number alterations in pediatric cancer models.Nature genetics · 2026Article
- A MAGIBU-based model for pediatric and juvenile CNS tumors: an in-house epigenetic decision-support framework compared with online DNA methylation classifiers.Free neuropathology · 2026Article
- Case Report: Identification of rareFrontiers in oncology · 2026Article
- Limitations of DNA Methylation Profiling in High-Grade Gliomas: Case Series.Diagnostics (Basel, Switzerland) · 2025Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
57 authors.
Dominik SturmHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0003-0250-1696
David CapperDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0003-1945-497X
Felipe AndreiuoloDepartment of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-2568-6155
Marco GessiDepartment of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany.
Christian KölscheInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-8763-8864
Annekathrin ReinhardtDepartment of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
Philipp SieversDepartment of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.ORCID http://orcid.org/0000-0003-3237-6021
Annika K WefersInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID http://orcid.org/0000-0001-9394-8519
Azadeh EbrahimiDepartment of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0001-7354-1746
Abigail K SuwalaDepartment of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
Gerrit H GielenDepartment of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-2707-0290
Martin SillHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Daniel SchrimpfDepartment of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
Damian StichelDepartment of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
Volker HovestadtDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Bjarne DaenekasDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-0237-8694
Agata RodeHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Stefan HamelmannDepartment of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
Christopher PrevitiHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Natalie JägerHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Ivo BuchhalterOmics IT and Data Management Core Facility, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
Mirjam Blattner-JohnsonHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Barbara C JonesHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Monika Warmuth-MetzDepartment of Diagnostic and Interventional Neuroradiology, University Hospital of Würzburg, Würzburg, Germany.
Brigitte BisonNeuroradiological Reference Center for the Pediatric Brain Tumor (HIT) Studies of the German Society of Pediatric Oncology and Hematology, University Hospital Würzburg, since 2021 University Hospital Augsburg, Augsburg, Germany.
Kerstin GrundInstitute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany.
Christian SutterInstitute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany.
Steffen HirschHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Nicola DikowInstitute of Human Genetics, Heidelberg University Hospital, Heidelberg, Germany.
Martin HasselblattInstitute of Neuropathology, University Hospital Münster, Münster, Germany.
Ulrich SchüllerInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID http://orcid.org/0000-0002-8731-1121
Arend KochDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Nicolas U GerberDepartment of Oncology, University Children's Hospital Zürich, Zürich, Switzerland.
Christine L WhiteGenetics and Molecular Pathology Laboratory, Hudson Institute of Medical Research, Clayton, VIC, Australia.ORCID http://orcid.org/0000-0002-5920-0029
Molly K BuntineGenetics and Molecular Pathology Laboratory, Hudson Institute of Medical Research, Clayton, VIC, Australia.
Kathryn KinrossAustralian and New Zealand Children's Haematology and Oncology Group (ANZCHOG), Hudson Institute of Medical Research, Clayton, VIC, Australia.
Elizabeth M AlgarGenetics and Molecular Pathology Laboratory, Hudson Institute of Medical Research, Clayton, VIC, Australia.ORCID http://orcid.org/0000-0002-9875-8092
Jordan R HansfordWomen's and Children's Hospital, South Australia Health and Medical Research Institute, South Australia immunoGENomics Cancer Institute, University of Adelaide, Adelaide, SA, Australia.ORCID http://orcid.org/0000-0001-7733-383X
Nicholas G GottardoDepartment of Paediatric and Adolescent Oncology/Haematology, Perth Children's Hospital, Nedlands, WA, Australia.ORCID http://orcid.org/0000-0002-1082-6776
Martin U SchuhmannDepartment of Neurosurgery, University of Tuebingen, Tuebingen, Germany.
Ulrich W ThomaleDepartment of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Pablo Hernáiz DrieverGerman HIT-LOGGIC Registry for low-grade glioma in children and adolescents, Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0003-3135-3872
Astrid GnekowSwabian Children's Cancer Center, Paediatric and Adolescent Medicine, Faculty of Medicine, University Augsburg, Augsburg, Germany.ORCID http://orcid.org/0000-0002-7356-6887
Olaf WittHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Hermann L MüllerDepartment of Pediatrics and Pediatric Hematology/Oncology, University Children's Hospital, Klinikum Oldenburg AöR, Oldenburg, Germany.ORCID http://orcid.org/0000-0003-4929-9966
Gabriele CalaminusDepartment of Pediatric Hematology and Oncology, University Childrens' Hospital Muenster, Muenster, Germany.
Gudrun FleischhackPediatric Hematology and Oncology, Pediatrics III, University Children's Hospital of Essen, Essen, Germany.ORCID http://orcid.org/0000-0001-5714-007X
Uwe KordesDepartment of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID http://orcid.org/0000-0001-6375-2320
Martin MynarekDepartment of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID http://orcid.org/0000-0003-3302-2719
Stefan RutkowskiDepartment of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Michael C FrühwaldSwabian Children's Cancer Center, Paediatric and Adolescent Medicine, Faculty of Medicine, University Augsburg, Augsburg, Germany.ORCID http://orcid.org/0000-0002-8237-1854
Christof M KrammDepartment of Child and Adolescent Health, Division of Pediatric Hematology and Oncology, University Medical Center Göttingen, Göttingen, Germany.ORCID http://orcid.org/0000-0002-5017-926X
Andreas von DeimlingDepartment of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.ORCID http://orcid.org/0000-0002-5863-540X
Torsten PietschDepartment of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn, Bonn, Germany.
Felix SahmHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Stefan M PfisterHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
David T W JonesHopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany. david.jones@kitz-heidelberg.de.ORCID http://orcid.org/0000-0002-2036-5141
Funding
No grant is acknowledged in the PubMed record.
Abstract
The large diversity of central nervous system (CNS) tumor types in children and adolescents results in disparate patient outcomes and renders accurate diagnosis challenging. In this study, we prospectively integrated DNA methylation profiling and targeted gene panel sequencing with blinded neuropathological reference diagnostics for a population-based cohort of more than 1,200 newly diagnosed pediatric patients with CNS tumors, to assess their utility in routine neuropathology. We show that the multi-omic integration increased diagnostic accuracy in a substantial proportion of patients through annotation to a refining DNA methylation class (50%), detection of diagnostic or therapeutically relevant genetic alterations (47%) or identification of cancer predisposition syndromes (10%). Discrepant results by neuropathological WHO-based and DNA methylation-based classification (30%) were enriched in histological high-grade gliomas, implicating relevance for current clinical patient management in 5% of all patients. Follow-up (median 2.5 years) suggests improved survival for patients with histological high-grade gliomas displaying lower-grade molecular profiles. These results provide preliminary evidence of the utility of integrating multi-omics in neuropathology for pediatric neuro-oncology.
Indexed as
Brain NeoplasmsGliomaAdolescentChildDNA MethylationHumansMultiomicsMutationNeuropathology
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