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DNA methylation-based classification of central nervous system tumours

Author

Listed:
  • David Capper

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ)
    Charité — Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
    German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ))

  • David T. W. Jones

    (Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
    German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Martin Sill

    (Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
    German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ)
    German Cancer Research Center (DKFZ))

  • Volker Hovestadt

    (German Cancer Research Center (DKFZ)
    Massachusetts General Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Daniel Schrimpf

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Dominik Sturm

    (Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
    German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ)
    Hematology and Immunology, University Hospital Heidelberg)

  • Christian Koelsche

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Felix Sahm

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Lukas Chavez

    (Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
    German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • David E. Reuss

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Annekathrin Kratz

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Annika K. Wefers

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Kristin Huang

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Kristian W. Pajtler

    (Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
    German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ)
    Hematology and Immunology, University Hospital Heidelberg)

  • Leonille Schweizer

    (University Hospital Heidelberg
    Charité — Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Damian Stichel

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Adriana Olar

    (Medical University of South Carolina
    Medical University of South Carolina
    Hollings Cancer Center)

  • Nils W. Engel

    (Hubertus Wald Tumorzentrum/University Cancer Center Hamburg, University Medical Center Hamburg
    Center for Neuropathology and Prion Research, Ludwig-Maximilians-University)

  • Kerstin Lindenberg

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

  • Patrick N. Harter

    (Institute of Neurology (Edinger Institute), Goethe-University Frankfurt am Main, Frankfurt am Main
    German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt am Main, German Cancer Research Center (DKFZ))

  • Anne K. Braczynski

    (Institute of Neurology (Edinger Institute), Goethe-University Frankfurt am Main, Frankfurt am Main
    German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt am Main, German Cancer Research Center (DKFZ))

  • Karl H. Plate

    (Institute of Neurology (Edinger Institute), Goethe-University Frankfurt am Main, Frankfurt am Main
    German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt am Main, German Cancer Research Center (DKFZ))

  • Hildegard Dohmen

    (Institute of Neuropathology, University of Giessen)

  • Boyan K. Garvalov

    (Institute of Neuropathology, University of Giessen)

  • Roland Coras

    (Neuropathological Institute, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg)

  • Annett Hölsken

    (Neuropathological Institute, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg)

  • Ekkehard Hewer

    (Institute of Pathology, University of Bern)

  • Melanie Bewerunge-Hudler

    (Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ))

  • Matthias Schick

    (Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ))

  • Roger Fischer

    (Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ))

  • Rudi Beschorner

    (Institute of Pathology and Neuropathology, University Hospital Tübingen)

  • Jens Schittenhelm

    (Institute of Pathology and Neuropathology, University Hospital Tübingen)

  • Ori Staszewski

    (Institute of Neuropathology, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg)

  • Khalida Wani

    (University of Texas MD Anderson Cancer Center)

  • Pascale Varlet

    (Centre Hospitalier Sainte Anne)

  • Melanie Pages

    (Centre Hospitalier Sainte Anne)

  • Petra Temming

    (Pediatrics III, Pediatric Oncology and Hematology, University Hospital Essen)

  • Dietmar Lohmann

    (Eye Cancer Research Group, Faculty of Medicine, University of Duisburg-Essen)

  • Florian Selt

    (Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
    Hematology and Immunology, University Hospital Heidelberg
    CCU Pediatric Oncology (G340), German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK))

  • Hendrik Witt

    (Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
    German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ)
    Hematology and Immunology, University Hospital Heidelberg)

  • Till Milde

    (Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
    Hematology and Immunology, University Hospital Heidelberg
    CCU Pediatric Oncology (G340), German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK))

  • Olaf Witt

    (Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
    Hematology and Immunology, University Hospital Heidelberg
    CCU Pediatric Oncology (G340), German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK))

  • Eleonora Aronica

    (Academic Medisch Centrum (AMC), University of Amsterdam
    Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam
    Stichting Epilepsie Instellingen Nederland (SEIN))

  • Felice Giangaspero

    (Oncological and Anatomo-Pathological Sciences, Sapienza University
    IRCCS Neuromed)

  • Elisabeth Rushing

    (University Hospital Zurich)

  • Wolfram Scheurlen

    (Cnopf’sche Kinderklinik Nuremberg)

  • Christoph Geisenberger

    (Heidelberg University Hospital
    Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences))

  • Fausto J. Rodriguez

    (Division of Neuropathology of the Johns Hopkins University School of Medicine)

  • Albert Becker

    (University of Bonn)

  • Matthias Preusser

    (Comprehensive Cancer Center Vienna, CNS Unit (CCC-CNS), Medical University of Vienna)

  • Christine Haberler

    (Institute of Neurology, Medical University of Vienna)

  • Rolf Bjerkvig

    (University of Bergen
    NORLUX Neuro-Oncology Laboratory, Luxembourg Institute of Health)

  • Jane Cryan

    (Beaumont Hospital)

  • Michael Farrell

    (Beaumont Hospital)

  • Martina Deckert

    (University Hospital of Cologne)

  • Jürgen Hench

    (Institute of Pathology, Basel University Hospital)

  • Stephan Frank

    (Institute of Pathology, Basel University Hospital)

  • Jonathan Serrano

    (NYU Langone Medical Center)

  • Kasthuri Kannan

    (NYU Langone Medical Center)

  • Aristotelis Tsirigos

    (NYU Langone Medical Center)

  • Wolfgang Brück

    (Institute of Neuropathology, University Medical Center Göttingen)

  • Silvia Hofer

    (Luzerner Kantonsspital)

  • Stefanie Brehmer

    (University Medical Center Mannheim, University of Heidelberg)

  • Marcel Seiz-Rosenhagen

    (University Medical Center Mannheim, University of Heidelberg)

  • Daniel Hänggi

    (University Medical Center Mannheim, University of Heidelberg)

  • Volkmar Hans

    (Institut für Neuropathologie, Evangelisches Krankenhaus Bielefeld gGmbH
    Institut für Neuropathologie, Universitätskinikum Essen)

  • Stephanie Rozsnoki

    (Institute of Neuropathology, University Hospital Münster)

  • Jordan R. Hansford

    (Children’s Cancer Centre, Royal Children’s Hospital, University of Melbourne, Melbourne
    Murdoch Children’s Research Institute, University of Melbourne
    University of Melbourne)

  • Patricia Kohlhof

    (Institute for Pathology, Katharinenhospital Stuttgart)

  • Bjarne W. Kristensen

    (Odense University Hospital, University of Southern Denmark)

  • Matt Lechner

    (University College London Cancer Institute and University College London Hospitals)

  • Beatriz Lopes

    (University of Virginia)

  • Christian Mawrin

    (Institute of Neuropathology, Otto-von-Guericke-University)

  • Ralf Ketter

    (University Hospital Saarland)

  • Andreas Kulozik

    (Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
    Hematology and Immunology, University Hospital Heidelberg)

  • Ziad Khatib

    (Nicklaus Children’s Hospital Brain Institute)

  • Frank Heppner

    (Charité — Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
    Cluster of Excellence, NeuroCure
    Berlin Institute of Health (BIH))

  • Arend Koch

    (Charité — Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Anne Jouvet

    (Hôpital Neurologique, Hospices Civils de Lyon)

  • Catherine Keohane

    (Cork University Hospital)

  • Helmut Mühleisen

    (Ludwigsburg Hospital)

  • Wolf Mueller

    (Leipzig University)

  • Ute Pohl

    (Queen’s Hospital)

  • Marco Prinz

    (Institute of Neuropathology, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg
    BIOSS Centre for Biological Signalling Studies, University of Freiburg)

  • Axel Benner

    (German Cancer Research Center (DKFZ))

  • Marc Zapatka

    (German Cancer Research Center (DKFZ))

  • Nicholas G. Gottardo

    (Princess Margaret Hospital for Children
    Telethon Kids Institute, University of Western Australia
    School of Paediatrics and Child Health, University of Western Australia)

  • Pablo Hernáiz Driever

    (Charité-Universitätsmedizin Berlin)

  • Christof M. Kramm

    (University Medical Center Göttingen)

  • Hermann L. Müller

    (Klinikum Oldenburg AöR, Medical Campus University Oldenburg)

  • Stefan Rutkowski

    (University Hospital Hamburg-Eppendorf)

  • Katja von Hoff

    (Charité-Universitätsmedizin Berlin
    University Hospital Hamburg-Eppendorf)

  • Michael C. Frühwald

    (Children’s Hospital Augsburg, Swabian Children’s Cancer Centre)

  • Astrid Gnekow

    (Children’s Hospital Augsburg, Swabian Children’s Cancer Centre)

  • Gudrun Fleischhack

    (Pediatrics III, Pediatric Oncology and Hematology, University Hospital Essen)

  • Stephan Tippelt

    (Pediatrics III, Pediatric Oncology and Hematology, University Hospital Essen)

  • Gabriele Calaminus

    (University of Bonn Medical Center)

  • Camelia-Maria Monoranu

    (Insitute of Pathology, Comprehensive Cancer Center (CCC) Mainfranken, University of Würzburg)

  • Arie Perry

    (University of California San Francisco)

  • Chris Jones

    (Institute of Cancer Research)

  • Thomas S. Jacques

    (Developmental Biology and Cancer Programme, Great Ormond Street Hospital for Children NHS Foundation Trust)

  • Bernhard Radlwimmer

    (German Cancer Research Center (DKFZ))

  • Marco Gessi

    (University of Bonn)

  • Torsten Pietsch

    (University of Bonn)

  • Johannes Schramm

    (Medical Faculty, University of Bonn Medical School)

  • Gabriele Schackert

    (University Hospital Carl Gustav Carus, Technische Universität Dresden)

  • Manfred Westphal

    (University Hospital Hamburg-Eppendorf)

  • Guido Reifenberger

    (Heinrich Heine University Düsseldorf
    German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, German Cancer Research Center (DKFZ))

  • Pieter Wesseling

    (Princess Máxima Center for Pediatric Oncology and University Medical Center Utrecht
    VU University Medical Center)

  • Michael Weller

    (University Hospital and University of Zurich)

  • Vincent Peter Collins

    (University of Cambridge)

  • Ingmar Blümcke

    (Neuropathological Institute, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg)

  • Martin Bendszus

    (Heidelberg University Hospital)

  • Jürgen Debus

    (Heidelberg University Hospital)

  • Annie Huang

    (Laboratory Medicine and Pathobiology, University of Toronto)

  • Nada Jabado

    (McGill University)

  • Paul A. Northcott

    (St Jude Children’s Research Hospital)

  • Werner Paulus

    (Institute of Neuropathology, University Hospital Münster)

  • Amar Gajjar

    (St Jude Children’s Research Hospital)

  • Giles W. Robinson

    (St Jude Children’s Research Hospital)

  • Michael D. Taylor

    (Arthur and Sonia Labatt Brain Tumor Research Centre, Hospital for Sick Children, University of Toronto)

  • Zane Jaunmuktane

    (UCL Hospitals, Institute of Neurology, University College London, Queen Square
    Institute of Neurology, University College London, Queen Square
    Institute of Neurology, University College London, Queen Square)

  • Marina Ryzhova

    (NN Burdenko Neurosurgical Institute)

  • Michael Platten

    (Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University)

  • Andreas Unterberg

    (Heidelberg University Hospital)

  • Wolfgang Wick

    (Heidelberg University Hospital)

  • Matthias A. Karajannis

    (Memorial Sloan Kettering Cancer Center)

  • Michel Mittelbronn

    (Institute of Neurology (Edinger Institute), Goethe-University Frankfurt am Main, Frankfurt am Main
    German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt am Main, German Cancer Research Center (DKFZ)
    NORLUX Neuro-Oncology Laboratory, Luxembourg Institute of Health (LIH)
    Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg)

  • Till Acker

    (Institute of Neuropathology, University of Giessen)

  • Christian Hartmann

    (Hannover Medical School (MHH))

  • Kenneth Aldape

    (University of Toronto)

  • Ulrich Schüller

    (Center for Neuropathology and Prion Research, Ludwig-Maximilians-University
    Institute of Neuropathology, University Medical Center, Hamburg-Eppendorf
    Research Institute Children’s Cancer Center
    University Medical Center, Hamburg-Eppendorf)

  • Rolf Buslei

    (Neuropathological Institute, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg
    Section Neuropathology, Institute of Pathology, Sozialstiftung Bamberg, Klinikum am Bruderwald)

  • Peter Lichter

    (German Cancer Research Center (DKFZ))

  • Marcel Kool

    (Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
    German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Christel Herold-Mende

    (Heidelberg University Hospital)

  • David W. Ellison

    (St Jude Children’s Research Hospital)

  • Martin Hasselblatt

    (Institute of Neuropathology, University Hospital Münster)

  • Matija Snuderl

    (NYU Langone Medical Center)

  • Sebastian Brandner

    (UCL Hospitals, Institute of Neurology, University College London, Queen Square
    Institute of Neurology, University College London, Queen Square)

  • Andrey Korshunov

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Andreas von Deimling

    (University Hospital Heidelberg
    Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ))

  • Stefan M. Pfister

    (Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ)
    German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ)
    Hematology and Immunology, University Hospital Heidelberg)

Abstract

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging—with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.

Suggested Citation

  • David Capper & David T. W. Jones & Martin Sill & Volker Hovestadt & Daniel Schrimpf & Dominik Sturm & Christian Koelsche & Felix Sahm & Lukas Chavez & David E. Reuss & Annekathrin Kratz & Annika K. We, 2018. "DNA methylation-based classification of central nervous system tumours," Nature, Nature, vol. 555(7697), pages 469-474, March.
    • Handle: RePEc:nat:nature:v:555:y:2018:i:7697:d:10.1038_nature26000
    DOI: 10.1038/nature26000
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    Cited by:

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    4. Maria Pouyiourou & Bianca N. Kraft & Timothy Wohlfromm & Michael Stahl & Boris Kubuschok & Harald Löffler & Ulrich T. Hacker & Gerdt Hübner & Lena Weiss & Michael Bitzer & Thomas Ernst & Philipp Schüt, 2023. "Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
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