Sarcoma classification by DNA methylation profiling View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-01-21

AUTHORS

Christian Koelsche, Daniel Schrimpf, Damian Stichel, Martin Sill, Felix Sahm, David E. Reuss, Mirjam Blattner, Barbara Worst, Christoph E. Heilig, Katja Beck, Peter Horak, Simon Kreutzfeldt, Elke Paff, Sebastian Stark, Pascal Johann, Florian Selt, Jonas Ecker, Dominik Sturm, Kristian W. Pajtler, Annekathrin Reinhardt, Annika K. Wefers, Philipp Sievers, Azadeh Ebrahimi, Abigail Suwala, Francisco Fernández-Klett, Belén Casalini, Andrey Korshunov, Volker Hovestadt, Felix K. F. Kommoss, Mark Kriegsmann, Matthias Schick, Melanie Bewerunge-Hudler, Till Milde, Olaf Witt, Andreas E. Kulozik, Marcel Kool, Laura Romero-Pérez, Thomas G. P. Grünewald, Thomas Kirchner, Wolfgang Wick, Michael Platten, Andreas Unterberg, Matthias Uhl, Amir Abdollahi, Jürgen Debus, Burkhard Lehner, Christian Thomas, Martin Hasselblatt, Werner Paulus, Christian Hartmann, Ori Staszewski, Marco Prinz, Jürgen Hench, Stephan Frank, Yvonne M. H. Versleijen-Jonkers, Marije E. Weidema, Thomas Mentzel, Klaus Griewank, Enrique de Álava, Juan Díaz Martín, Miguel A. Idoate Gastearena, Kenneth Tou-En Chang, Sharon Yin Yee Low, Adrian Cuevas-Bourdier, Michel Mittelbronn, Martin Mynarek, Stefan Rutkowski, Ulrich Schüller, Viktor F. Mautner, Jens Schittenhelm, Jonathan Serrano, Matija Snuderl, Reinhard Büttner, Thomas Klingebiel, Rolf Buslei, Manfred Gessler, Pieter Wesseling, Winand N. M. Dinjens, Sebastian Brandner, Zane Jaunmuktane, Iben Lyskjær, Peter Schirmacher, Albrecht Stenzinger, Benedikt Brors, Hanno Glimm, Christoph Heining, Oscar M. Tirado, Miguel Sáinz-Jaspeado, Jaume Mora, Javier Alonso, Xavier Garcia del Muro, Sebastian Moran, Manel Esteller, Jamal K. Benhamida, Marc Ladanyi, Eva Wardelmann, Cristina Antonescu, Adrienne Flanagan, Uta Dirksen, Peter Hohenberger, Daniel Baumhoer, Wolfgang Hartmann, Christian Vokuhl, Uta Flucke, Iver Petersen, Gunhild Mechtersheimer, David Capper, David T. W. Jones, Stefan Fröhling, Stefan M. Pfister, Andreas von Deimling

ABSTRACT

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. More... »

PAGES

498

References to SciGraph publications

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    12

    Author Affiliations

  • Department of General Pathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany
  • Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 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
  • 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
  • Clinical Cooperation Unit Pediatric Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
  • Genomics and Proteomics Core Facility, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany
  • Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany
  • Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany
  • Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), Heidelberg, Germany
  • Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany
  • Department of Orthopaedics, Trauma Surgery and Paraplegiology, Heidelberg University Hospital, Heidelberg, Germany
  • Institute of Neuropathology, University Hospital Münster, Münster, Germany
  • Department of Neuropathology, Institute of Pathology, Hannover Medical School (MHH), Hannover, Germany
  • Berta-Ottenstein-Programme for Clinician Scientists, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  • Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg, Germany
  • Department of Neuropathology, Institute of Pathology, Basel University Hospital, Basel, Switzerland
  • Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands
  • Dermatopathology Bodensee, Friedrichshafen, Germany
  • Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen, Essen, Germany
  • Department of Normal and Pathological Cytology and Histology, School of Medicine. University of Seville, Seville, Spain
  • Department of Pathology, Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital, CSIC/University of Sevilla/CIBERONC, Seville, Spain
  • Department of Pathological Anatomy, Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain
  • Department of Pathology and Laboratory Medicine, KK Women’s and Children’s Hospital, Singapore, Republic of Singapore
  • Department of Neurosurgery, National Neuroscience Institute, Singapore, Republic of Singapore
  • National Center of Pathology (NCP), Laboratoire National de Santé (LNS), Dudelange, Luxembourg
  • Department of Oncology (DONC), Luxembourg Institute of Health (LIH), Luxembourg, Luxembourg
  • Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Research Institute Children’s Cancer Center Hamburg, Hamburg, Germany
  • Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Department of Neuropathology, Institute of Pathology and Neuropathology, University Hospital of Tübingen, Tübingen, Germany
  • Department of Pathology, New York University School of Medicine, New York, NY, USA
  • Institute of Pathology, Cologne University Hospital, Cologne, Germany
  • Department of Pediatric Hematology and Oncology, University Children’s Hospital, Frankfurt/Main, Germany
  • Institute of Pathology, Sozialstiftung Bamberg, Klinikum am Bruderwald, Bamberg, Germany
  • Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Würzburg University, Würzburg, Germany
  • Department of Pathology, Amsterdam University Medical Centers/VUmc, Amsterdam, The Netherlands
  • Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
  • 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
  • Research Department of Pathology, University College London, London, UK
  • Division of Applied Bioinformatics, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
  • German Cancer Consortium (DKTK), Dresden, Germany
  • Sarcoma Research Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), CIBERONC, Barcelona, Catalonia, Spain
  • Department of Pediatric Onco-Hematology and Developmental Tumor Biology Laboratory, Hospital Sant Joan de Déu, Barcelona, Catalonia, Spain
  • Pediatric Solid Tumor Laboratory, Human Genetic Department, Research Institute of Rare Diseases, Instituto de Salud Carlos III (ISCIII), Madrid, Spain
  • Medical Oncology Service, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Barcelona, Catalonia, Spain
  • Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Catalonia, Spain
  • Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Catalonia, Spain
  • Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  • Gerhard Domagk Institute of Pathology, University Hospital Münster, Münster, Germany
  • University College London Cancer Institute, London, UK
  • International Ewing Sarcoma Study Group, German Cancer Consortium (DKTK), West German Cancer Center (WTZ), University Duisburg-Essen, Essen, Germany
  • Division of Surgical Oncology and Thoracic Surgery, Mannheim University Medical Center, University of Heidelberg, Mannheim, Germany
  • Bone Tumour Reference Centre at the Institute of Pathology, University Hospital Basel and University of Basel, Basel, Switzerland
  • Division of Translational Pathology, Gerhard Domagk Institute of Pathology, University Hospital Münster, Münster, Germany
  • Department of Pediatric Pathology, University Hospital of Schleswig-Holstein, Kiel, Germany
  • Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
  • Institute of Pathology, Jena, Jena University Hospital, Germany
  • Department of Neuropathology, Charité Universitätsmedizin Berlin, Berlin, Germany
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-020-20603-4

    DOI

    http://dx.doi.org/10.1038/s41467-020-20603-4

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33479225


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