Sarcoma classification by DNA methylation profiling.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
21 01 2021
Historique:
received: 23 03 2020
accepted: 08 12 2020
entrez: 22 1 2021
pubmed: 23 1 2021
medline: 9 2 2021
Statut: epublish

Résumé

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications.

Identifiants

pubmed: 33479225
doi: 10.1038/s41467-020-20603-4
pii: 10.1038/s41467-020-20603-4
pmc: PMC7819999
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

498

Subventions

Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA217694
Pays : United States
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Department of Health
ID : BRC399/NS/RB/101410
Pays : United Kingdom

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Auteurs

Christian Koelsche (C)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of General Pathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

Daniel Schrimpf (D)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Damian Stichel (D)

Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Martin Sill (M)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Felix Sahm (F)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

David E Reuss (DE)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Mirjam Blattner (M)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Pediatric Glioma Research Group, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Barbara Worst (B)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Pediatric Glioma Research Group, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Christoph E Heilig (CE)

Division of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.

Katja Beck (K)

Division of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
Heidelberg Center for Personalized Oncology (HIPO), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Peter Horak (P)

Division of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.

Simon Kreutzfeldt (S)

Division of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.

Elke Paff (E)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Pediatric Glioma Research Group, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Sebastian Stark (S)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Pediatric Glioma Research Group, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Pascal Johann (P)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Pediatric Glioma Research Group, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Florian Selt (F)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Jonas Ecker (J)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Dominik Sturm (D)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Pediatric Glioma Research Group, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Kristian W Pajtler (KW)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Annekathrin Reinhardt (A)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Annika K Wefers (AK)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Philipp Sievers (P)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Azadeh Ebrahimi (A)

Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Abigail Suwala (A)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Francisco Fernández-Klett (F)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Belén Casalini (B)

Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Andrey Korshunov (A)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Volker Hovestadt (V)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Felix K F Kommoss (FKF)

Department of General Pathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

Mark Kriegsmann (M)

Department of General Pathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

Matthias Schick (M)

Genomics and Proteomics Core Facility, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Melanie Bewerunge-Hudler (M)

Genomics and Proteomics Core Facility, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Till Milde (T)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Olaf Witt (O)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Andreas E Kulozik (AE)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Marcel Kool (M)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Laura Romero-Pérez (L)

Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany.

Thomas G P Grünewald (TGP)

Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany.

Thomas Kirchner (T)

Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany.

Wolfgang Wick (W)

Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Michael Platten (M)

Department of Neurology, Mannheim University Medical Center, University of Heidelberg, Mannheim, Germany.
Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Andreas Unterberg (A)

Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany.

Matthias Uhl (M)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), Heidelberg, Germany.

Amir Abdollahi (A)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), Heidelberg, Germany.
Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany.
Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Jürgen Debus (J)

Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.
Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), Heidelberg, Germany.
Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany.
Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Burkhard Lehner (B)

Department of Orthopaedics, Trauma Surgery and Paraplegiology, Heidelberg University Hospital, Heidelberg, Germany.

Christian Thomas (C)

Institute of Neuropathology, University Hospital Münster, Münster, Germany.

Martin Hasselblatt (M)

Institute of Neuropathology, University Hospital Münster, Münster, Germany.

Werner Paulus (W)

Institute of Neuropathology, University Hospital Münster, Münster, Germany.

Christian Hartmann (C)

Department of Neuropathology, Institute of Pathology, Hannover Medical School (MHH), Hannover, Germany.

Ori Staszewski (O)

Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Berta-Ottenstein-Programme for Clinician Scientists, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Marco Prinz (M)

Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Signalling Research Centers BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Jürgen Hench (J)

Department of Neuropathology, Institute of Pathology, Basel University Hospital, Basel, Switzerland.

Stephan Frank (S)

Department of Neuropathology, Institute of Pathology, Basel University Hospital, Basel, Switzerland.

Yvonne M H Versleijen-Jonkers (YMH)

Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.

Marije E Weidema (ME)

Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.

Thomas Mentzel (T)

Dermatopathology Bodensee, Friedrichshafen, Germany.

Klaus Griewank (K)

Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen, Essen, Germany.

Enrique de Álava (E)

Department of Pathology, Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital, CSIC/University of Sevilla/CIBERONC, Seville, Spain.
Department of Normal and Pathological Cytology and Histology, School of Medicine. University of Seville, Seville, Spain.

Juan Díaz Martín (JD)

Department of Pathology, Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital, CSIC/University of Sevilla/CIBERONC, Seville, Spain.

Miguel A Idoate Gastearena (MAI)

Department of Pathological Anatomy, Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain.

Kenneth Tou-En Chang (KT)

Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore, Republic of Singapore.

Sharon Yin Yee Low (SYY)

Department of Neurosurgery, National Neuroscience Institute, Singapore, Republic of Singapore.

Adrian Cuevas-Bourdier (A)

National Center of Pathology (NCP), Laboratoire National de Santé (LNS), Dudelange, Luxembourg.

Michel Mittelbronn (M)

National Center of Pathology (NCP), Laboratoire National de Santé (LNS), Dudelange, Luxembourg.
Luxembourg Center of Neuropathology (LCNP), Luxembourg, Luxembourg.
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Luxembourg, Luxembourg.
Department of Oncology (DONC), Luxembourg Institute of Health (LIH), Luxembourg, Luxembourg.

Martin Mynarek (M)

Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Stefan Rutkowski (S)

Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Ulrich Schüller (U)

Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.

Viktor F Mautner (VF)

Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Jens Schittenhelm (J)

Department of Neuropathology, Institute of Pathology and Neuropathology, University Hospital of Tübingen, Tübingen, Germany.

Jonathan Serrano (J)

Department of Pathology, New York University School of Medicine, New York, NY, USA.

Matija Snuderl (M)

Department of Pathology, New York University School of Medicine, New York, NY, USA.

Reinhard Büttner (R)

Institute of Pathology, Cologne University Hospital, Cologne, Germany.

Thomas Klingebiel (T)

Department of Pediatric Hematology and Oncology, University Children's Hospital, Frankfurt/Main, Germany.

Rolf Buslei (R)

Institute of Pathology, Sozialstiftung Bamberg, Klinikum am Bruderwald, Bamberg, Germany.

Manfred Gessler (M)

Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Würzburg University, Würzburg, Germany.

Pieter Wesseling (P)

Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Department of Pathology, Amsterdam University Medical Centers/VUmc, Amsterdam, The Netherlands.

Winand N M Dinjens (WNM)

Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

Sebastian Brandner (S)

Department of Neurodegeneration, Institute of Neurology, University College London, London, UK.
Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK.

Zane Jaunmuktane (Z)

Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK.
Department of Molecular Neuroscience, UCL Queen Square Institute of Neurology, University College London, London, UK.

Iben Lyskjær (I)

Research Department of Pathology, University College London, London, UK.

Peter Schirmacher (P)

Department of General Pathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

Albrecht Stenzinger (A)

Department of General Pathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

Benedikt Brors (B)

Division of Applied Bioinformatics, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Hanno Glimm (H)

Translational and Functional Cancer Genomics, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), Dresden, Germany.
Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus Dresden at TU Dresden, Dresden, Germany.
German Cancer Consortium (DKTK), Dresden, Germany.

Christoph Heining (C)

Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ), Dresden, Germany.
Center for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus Dresden at TU Dresden, Dresden, Germany.
German Cancer Consortium (DKTK), Dresden, Germany.

Oscar M Tirado (OM)

Sarcoma Research Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), CIBERONC, Barcelona, Catalonia, Spain.

Miguel Sáinz-Jaspeado (M)

Sarcoma Research Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), CIBERONC, Barcelona, Catalonia, Spain.

Jaume Mora (J)

Department of Pediatric Onco-Hematology and Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Barcelona, Catalonia, Spain.

Javier Alonso (J)

Pediatric Solid Tumor Laboratory, Human Genetic Department, Research Institute of Rare Diseases, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.

Xavier Garcia Del Muro (XG)

Medical Oncology Service, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Barcelona, Catalonia, Spain.

Sebastian Moran (S)

Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain.

Manel Esteller (M)

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.

Jamal K Benhamida (JK)

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Marc Ladanyi (M)

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Eva Wardelmann (E)

Gerhard Domagk Institute of Pathology, University Hospital Münster, Münster, Germany.

Cristina Antonescu (C)

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Adrienne Flanagan (A)

Department of Histopathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, UK.
University College London Cancer Institute, London, UK.

Uta Dirksen (U)

Pediatrics III Pediatric Hematology, Oncology, Immunology, Cardiology, Pulmonology, West German Cancer Center, University Hospital Essen, Essen, Germany.
International Ewing Sarcoma Study Group, German Cancer Consortium (DKTK), West German Cancer Center (WTZ), University Duisburg-Essen, Essen, Germany.

Peter Hohenberger (P)

Division of Surgical Oncology and Thoracic Surgery, Mannheim University Medical Center, University of Heidelberg, Mannheim, Germany.

Daniel Baumhoer (D)

Bone Tumour Reference Centre at the Institute of Pathology, University Hospital Basel and University of Basel, Basel, Switzerland.

Wolfgang Hartmann (W)

Division of Translational Pathology, Gerhard Domagk Institute of Pathology, University Hospital Münster, Münster, Germany.

Christian Vokuhl (C)

Department of Pediatric Pathology, University Hospital of Schleswig-Holstein, Kiel, Germany.

Uta Flucke (U)

Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.

Iver Petersen (I)

Institute of Pathology, SRH Poliklinik Gera GmbH, Gera, Germany.
Institute of Pathology, Jena University Hospital, Jena, Germany.

Gunhild Mechtersheimer (G)

Department of General Pathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.

David Capper (D)

Department of Neuropathology, Charité Universitätsmedizin Berlin, Berlin, Germany.

David T W Jones (DTW)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Pediatric Glioma Research Group, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Stefan Fröhling (S)

Division of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.

Stefan M Pfister (SM)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Andreas von Deimling (A)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany. andreas.vondeimling@med.uni-heidelberg.de.
Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. andreas.vondeimling@med.uni-heidelberg.de.

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