Advancing sarcoma diagnostics with expanded DNA methylation-based classification
Abstract
Purpose: Sarcomas pose a severe diagnostic challenge. A wide variety of these distinct entities need to be distinguished from each other and from less aggressive types of mesenchymal tumors, to ensure correct clinical management. A machine learning based classifier for sarcomas utilizing DNA methylation data from 1077 tumors recognizing 62 sarcoma types has already been developed and termed the sarcoma classifier, which we published in 2021. Here we present a major advancement of the scale and precision of the sarcoma classifier. Methods: DNA methylation profiles and histologic data from an unprecedented multi-institutional cohort of mesenchymal tumors were collected and analyzed. Utilizing a machine learning approach, the classifier was rigorously validated through five-fold nested cross-validation, achieving a 98% class-level accuracy and a Brier score of 0.017, indicative of well-calibrated probability estimates. Results: The sarcoma classifier v13.1 was developed based on a training set of 4377 methylation profiles from sarcomas and less aggressive mesenchymal tumors comprising 116 tumor sub-classes and 4 control groups forming 93 distinct methylation classes. Performance was validated using four independent cohorts, comprising a total of 1547 mesenchymal tumors. A methylation-based classifier prediction was obtained in 73% of cases in the validation sets, of which 91% matched the original histopathology diagnosis, thereby increasing diagnostic confidence. The classifier enabled a definitive molecular diagnosis or tumor reclassification in 6% of cases with inconclusive or ambiguous histological findings. Conclusion: Adding new sarcoma types and expanding tumor sample numbers in each methylation class in the new sarcoma classifier decisively increased the number of diagnostic predictions and improved match with histologic evaluation. This substantial advancement will promote clinical implementation of the tool for the diagnosis of mesenchymal tumor lesions.
Authors 96
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Natalie Jäger corresponding
German Cancer Research Center · Hopp Children's Cancer Center Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany
Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
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German Cancer Research Center · Hopp Children's Cancer Center Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany
Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Hopp Children's Cancer Center Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany
Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · National Center for Tumor Diseases · Hopp Children's Cancer Center Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
National Center for Tumor Diseases Heidelberg (NCT), Heidelberg, Germany
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Affiliation as printed
Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany
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University Medical Center Groningen · Amsterdam UMC Location University of Amsterdam · Amsterdam University Medical Centers
Affiliation as printed
Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, the Netherlands
Department of Pathology, Amsterdam University Medical Centers, Amsterdam, the Netherlands
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Institució Catalana de Recerca i Estudis Avançats · Josep Carreras Leukaemia Research Institute · Centro de Investigación Biomédica en Red de Cáncer · Universitat de Barcelona
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Cancer Epigenetics Group, Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Catalonia, Spain
Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain
Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain
Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Catalonia, Spain
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German Cancer Research Center · Nationales Centrum für Tumorerkrankungen Dresden · German Cancer Consortium (DKTK) Dresden · Technische Universität Dresden
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German Cancer Consortium (DKTK), Dresden, Germany
Translational Functional Cancer Genomics, DKFZ, Heidelberg, Germany
Translational Medical Oncology, National Center for Tumor Diseases Dresden (NCT/UCC), Technical University Dresden and Helmholtz-Zentrum Dresden
Translational Medical Oncology, Technical University Dresden, 01307, Dresden, Germany
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Affiliation as printed
Gerhard-Domagk-Institute of Pathology, University of Münster, Münster, Germany
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Affiliation as printed
Division of Translational Medical Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Affiliation as printed
Division of Translational Medical Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · National Center for Tumor Diseases · Hopp Children's Cancer Center Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany
Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany
Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
National Center for Tumor Diseases Heidelberg (NCT), Heidelberg, Germany
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Affiliation as printed
Institute of Pathology, Waldklinikum Gera, Gera, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · National Center for Tumor Diseases · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neurology, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany
National Center for Tumor Diseases Heidelberg (NCT), Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · National Center for Tumor Diseases · Hopp Children's Cancer Center Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany
Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany
Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
National Center for Tumor Diseases Heidelberg (NCT), Heidelberg, Germany
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Université de Tours · Centre Hospitalier Universitaire de Tours
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CARADERM Network, Lille, France
Department of Pathology, Centre Hospitalier Universitaire de Tours, Université de Tours, Tours, France
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Bambino Gesù Children's Hospital
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Onco-Hematology, Cell Therapy, Gene Therapies and Hemopoietic Transplant, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
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NYU Langone Health · New York University
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Department of Pathology, NYU Langone Health and NYU Grossman School of Medicine, New York, New York, USA
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University of Basel · University Hospital of Basel
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Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
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Affiliation as printed
Department of Obstetrics & Gynecology and Diagnostic-und Research Institute of Pathology, Medical University of Graz, Austria
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Centre National de la Recherche Scientifique · Inserm · Institut pour l'avancée des biosciences · Université Grenoble Alpes
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Grenoble Alpes University Hospital Pathology Department, Institute for Advanced Biosciences UGA/INSERM U1209/CNRS 5309, Grenoble Alpes University, Grenoble, France
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · Hopp Children's Cancer Center Heidelberg
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Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
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Inserm · Centre Hospitalier Sainte-Anne · Institut Curie
Affiliation as printed
GHU-Paris - Sainte-Anne Hospital, Department of Neuropathology, Paris University, Paris, France
Institut Curie, Paris Sciences Lettres University, SIREDO, INSERM U830, Laboratory of Translational Research in Paediatric Oncology, Paris, France
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Centre Hospitalier Sainte-Anne
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Department of Neuropathology, GHU Paris - Psychiatry and Neuroscience, Sainte-Anne Hospital, Paris, 75014, France
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Affiliation as printed
Department of Dermatology, University of Heidelberg, Heidelberg, Germany
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University of Southern Denmark · Odense University Hospital
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Department of Clinical Research and BRIDGE, University of Southern Denmark, 5000 Odense, Denmark
Department of Pathology, Odense University Hospital, 5000 Odense, Denmark
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Affiliation as printed
Bioptical Laboratory, Ltd, Pilsen, Czech Republic
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University College London Hospitals NHS Foundation Trust · National Hospital for Neurology and Neurosurgery · UCL Queen Square Institute of Neurology · University College London
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Department of Neurodegenerative Diseases, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK
Division of Neuropathology, University College London Hospitals NHS Foundation Trust, Queen Square, London WC1N 3BG, UK
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Universidade Estadual de Campinas (UNICAMP) · Centro Infantil Boldrini
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Genetics and Molecular Biology, Institute of Biology, State University of Campinas, Campinas 13083-862, SP, Brazil
Research Center, Boldrini Children’s Hospital, Campinas 13083-884, SP, Brazil
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Centre National de la Recherche Scientifique · Inserm · Centre Hospitalier Universitaire de Toulouse · Centre de Recherches en Cancérologie de Toulouse · Université de Toulouse
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Pathology Department, Toulouse University Hospital, Toulouse, France
Toulouse University , Inserm, CNRS, Centre de Recherches en Cancérologie de Toulouse, Toulouse, France
UFR Santé, Université de Toulouse, Toulouse, France
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Great Ormond Street Hospital for Children NHS Foundation Trust
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Specialist Integrated Haematology and Malignancy Diagnostic Service-Acquired Genomics, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
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University Hospital Frankfurt · Institut für Neuropathologie · Ludwig-Maximilians-Universität München
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Institute of Neuropathology, Faculty of Medicine, LMU Munich, Munich, Germany
Neurological Institute (Edinger Institute), University Hospital Frankfurt, Frankfurt am Main, Germany
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Assistance Publique Hôpitaux de Marseille · Hôpital de la Timone
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Department of Pathological Anatomy and Neuropathology, Timone Hospital, APHM, Marseille, France
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Affiliation as printed
Institute of Pathology, Center for Molecular Pathology Diagnosis, University of Regensburg, Regensburg, Germany
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University of Münster · University Hospital Münster
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Institute of Neuropathology, University Hospital Münster, Pottkamp 2, 48149, Münster, Germany
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Radboud University Medical Center · Princess Máxima Center
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Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
Diagnostic Laboratory, Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
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University Medical Center Utrecht · Princess Máxima Center
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Princess Maxima Center and UMC Utrecht, The Netherlands
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Affiliation as printed
Division of Neuropathology, University Hospital Leipzig, 04103, Leipzig, Germany
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Inserm · Université Paris Cité · Centre Hospitalier Sainte-Anne · Institut de Psychiatrie et Neurosciences de Paris · Institut Curie
Affiliation as printed
Department of Neuropathology, GHU Paris - Psychiatry and Neuroscience, Sainte-Anne Hospital, Paris, 75014, France
Institut de Psychiatrie et Neurosciences de Paris (IPNP), UMR S1266, INSERM, IMA-BRAIN, Paris, France
Laboratory of Somatic Genetics, Université de Paris, France3 Curie Institute Hospital, Paris, Paris, France
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Heidelberg University · University Hospital Heidelberg · Klinikum Ludwigsburg
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Department of Pathology, Heidelberg University Hospital, Heidelberg, Germany
Institute of Pathology and Neuropathology, RKH Klinikum Ludwigsburg, Ludwigsburg, Germany
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TUM Klinikum · Technical University of Munich
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Children’s Cancer Research Centre and Department of Pediatrics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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Olgahospital · Klinikum Stuttgart
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Klinikum Stuttgart - Olgahospital, Zentrum für Kinder-, Jugend-und Frauenmedizin, Pädiatrie, Stuttgart, Germany
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Affiliation as printed
Klinikum der Landeshauptstadt Stuttgart gKAöR, Olgahospital, Stuttgart Cancer Center, Zentrum für Kinder-, Jugend-und Frauenmedizin, Pädiatrie 5 (Pädiatrische Onkologie, Hämatologie, Immunologie), Stuttgart, Germany
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University of Luxembourg · Luxembourg Institute of Health · Luxembourg Centre for Systems Biomedicine
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Department of Cancer Research (DoCR), Luxembourg Institute of Health (LIH), 1210 Luxembourg, Luxembourg
Department of Life Sciences and Medicine (DLSM), University of Luxembourg, 4365 Esch-sur- Alzette, Luxembourg
Luxembourg Center of Neuropathology (LCNP), 3555 Dudelange, Luxembourg
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg (UL), 4362 Esch- sur-Alzette, Luxembourg
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Dermatopathologie Friedrichshafen
Affiliation as printed
Dermatopathology Friedrichshafen, Friedrichshafen, Germany
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Affiliation as printed
Department of Neurosurgery, University Medicine Halle, Halle, Germany
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Affiliation as printed
Cure NF Research Group, Anatomy and Cell Biology, University Medicine Halle, Halle, Germany
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Justus-Liebig-Universität Gießen
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Institute of Neuropathology, Justus-Liebig University Giessen, Giessen, Germany
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National Institutes of Health · National Cancer Institute
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Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, USA
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Affiliation as printed
Gerhard-Domagk-Institute of Pathology, University of Münster, Münster, Germany
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Memorial Sloan Kettering Cancer Center
Affiliation as printed
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York, USA
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Memorial Sloan Kettering Cancer Center
Affiliation as printed
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York, USA
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Deutsches Konsortium für Translationale Krebsforschung · Pathologisches Institut · Ludwig-Maximilians-Universität München
Affiliation as printed
German Cancer Consortium (DKTK), Munich, Germany
Institute of Pathology, Ludwig Maximilians University Hospital Munich, 80336 Munich, Germany
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Affiliation as printed
Department of Human Genetics, McGill University, Montreal, Quebec, Canada
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Affiliation as printed
Children’s Cancer Institute, Lowy Cancer Research Centre, UNSW, Kensington, NSW, Australia
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University of Basel · University Hospital of Basel
Affiliation as printed
Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
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Radboud University Medical Center
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Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands
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Radboud University Nijmegen · Radboud University Medical Center
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Department of Medical Oncology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
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Heidelberg University · University Hospital Heidelberg
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Department of Pathology, Heidelberg University Hospital, Heidelberg, Germany
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Heidelberg University · University Hospital Heidelberg
Affiliation as printed
Department of Neurosurgery, University Hospital Heidelberg, Heidelberg University, 69117 Heidelberg, Germany
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University of Würzburg · Comprehensive Cancer Center Mainfranken
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Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Wuerzburg, Germany
Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, University of Wuerzburg, Wuerzburg, Germany
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University of Basel · University Hospital of Basel
Affiliation as printed
Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
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University of Cambridge · Cambridge University Hospitals NHS Foundation Trust · Wellcome Sanger Institute
Affiliation as printed
Cambridge University Hospitals NHS Foundation Trust; Cambridge, CB2 0QQ, UK
Department of Paediatrics, University of Cambridge; Cambridge, UK
Wellcome Sanger Institute; Hinxton, CB10 1SA, UK
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Affiliation as printed
Pathology Unit, Department of Laboratory Medicine, Department of Medical Sciences, University of Turin, Turin, Italy
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Essen University Hospital · Deutsches Konsortium für Translationale Krebsforschung · University of Duisburg-Essen
Affiliation as printed
Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Germany & German Cancer Consortium (Deutsches Konsortium für Translationale Krebsforschung, DKTK), Essen, Germany
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Essen University Hospital · Deutsches Konsortium für Translationale Krebsforschung · University of Duisburg-Essen
Affiliation as printed
Comprehensive Cancer Center (Westdeutsches Tumorzentrum), University Hospital Essen, Essen & National Center for Tumor Diseases (NCT) West, Essen, Germany
Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Germany & German Cancer Consortium (Deutsches Konsortium für Translationale Krebsforschung, DKTK), Essen, Germany
Research Center One Health, University Duisburg-Essen, Essen, Germany
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
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Université Paris-Saclay · Assistance Publique – Hôpitaux de Paris · Hôpital Ambroise-Paré · Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie
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Paris-Saclay University, Versailles SQY University, EA4340-BECCOH, Assistance Publique– Hôpitaux de Paris (AP-HP), Ambroise-Paré Hospital, Smart Imaging, Service de Pathologie, Boulogne, France
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Leiden University Medical Center
Affiliation as printed
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands
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Charité - Universitätsmedizin Berlin
Affiliation as printed
Institute of Pathology, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Affiliation as printed
Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Frankfurt, Germany
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Technische Universität Dresden
Affiliation as printed
Institute of Pathology, Technical University Dresden, 01307, Dresden, Germany
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Technische Universität Dresden
Affiliation as printed
Institute of Pathology, Technical University Dresden, 01307, Dresden, Germany
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Technische Universität Dresden
Affiliation as printed
Institute of Pathology, Technical University Dresden, 01307, Dresden, Germany
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Technische Universität Dresden
Affiliation as printed
Institute of Pathology, Technical University Dresden, 01307, Dresden, Germany
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Affiliation as printed
Department of Pathology and Laboratory Medicine, King Hussein Cancer Center, Amman, Jordan
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National Institutes of Health · National Cancer Institute
Affiliation as printed
Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, USA
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Queen Mary Hospital · University of Hong Kong
Affiliation as printed
Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong
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University Children's Hospital Zurich
Affiliation as printed
University Children’s Hospital, Oncology, Balgrist Campus, Zurich, Switzerland
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University of Bern · University Hospital of Bern
Affiliation as printed
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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Heidelberg University · University Hospital Heidelberg
Affiliation as printed
Department of Pathology, Heidelberg University Hospital, Heidelberg, Germany
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National Institutes of Health · National Cancer Institute
Affiliation as printed
Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, USA
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National Institutes of Health · National Cancer Institute
Affiliation as printed
Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, USA
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Royal National Orthopaedic Hospital · Royal National Orthopaedic Hospital NHS Trust · University College London
Affiliation as printed
The Royal National Orthopaedic Hospital Trust, Brockley Hill, Stanmore HA7 4LP, UK
UCL Cancer Institute, London WC1E 6DD, UK
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Affiliation as printed
Pediatric Oncology & Hematology, Pediatrics III, University Hospital of Essen, Essen, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · National Center for Tumor Diseases · Hopp Children's Cancer Center Heidelberg
Affiliation as printed
Division of Pediatric Neurooncology, Hopp Children’s Cancer Center Heidelberg (KiTZ); German Cancer Research Center Heidelberg (DKFZ) and Heidelberg University Hospital, Heidelberg; National Center for Tumor Diseases (NCT), Heidelberg, Germany
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German Cancer Research Center · Heidelberg University · University Hospital Heidelberg · National Center for Tumor Diseases · Hopp Children's Cancer Center Heidelberg · Deutsches Konsortium für Translationale Krebsforschung
Affiliation as printed
Department of Pathology, Heidelberg University Hospital, Heidelberg, Germany
Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany
National Center for Tumor Diseases Heidelberg (NCT), Heidelberg, Germany
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