DNA methylation-based classification of central nervous system tumours

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 i...

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Published in	Nature (London) Vol. 555; no. 7697; pp. 469 - 474
Main Authors	Capper, David, Jones, David T. W., Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Kratz, Annekathrin, Huang, Kristin, Pajtler, Kristian W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Hölsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Schittenhelm, Jens, Wani, Khalida, Witt, Hendrik, Milde, Till, Witt, Olaf, Giangaspero, Felice, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Jürgen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brück, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Hänggi, Daniel, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Mühleisen, Helmut, Mueller, Wolf, Driever, Pablo Hernáiz, Kramm, Christof M., Müller, Hermann L., Rutkowski, Stefan, Frühwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Calaminus, Gabriele, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Bendszus, Martin, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Taylor, Michael D., Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Korshunov, Andrey, Pfister, Stefan M.
Format	Journal Article
Language	English
Published	London Nature Publishing Group UK 22.03.2018 Nature Publishing Group
Subjects	13/56 45/61 631/114/1386 631/114/2407 631/67/1922 631/67/69 Adolescent Adult Aged Aged, 80 and over Bioinformatics Brain cancer Cancer Cancer diagnosis Central nervous system Central Nervous System Neoplasms - classification Central Nervous System Neoplasms - diagnosis Central Nervous System Neoplasms - genetics Central Nervous System Neoplasms - pathology Child Child, Preschool Classification Classifiers Clinical trials Cohort Studies Data processing Deoxyribonucleic acid Diagnosis Diagnostic software Diagnostic systems DNA DNA Methylation DNA sequencing Female Gene expression Generalized linear models Genetic aspects Genomes Humanities and Social Sciences Humans Identification and classification Infant Learning algorithms Machine learning Male Medical examination Methods Methylation Middle Aged multidisciplinary Nervous system Observations Probability Reproducibility of Results Science Standardization Tumors Unsupervised Machine Learning Young Adult Germany
Online Access	Get full text
ISSN	0028-0836 1476-4687 1476-4687
DOI	10.1038/nature26000

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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. An online approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups has been developed to help to improve current diagnostic standards. Classifying tumour types for better diagnoses Precise cancer diagnoses are essential to ensure the best treatment plans for patients, but standardization of the diagnostic process has been challenging. The authors present a comprehensive approach for DNA-methylation-based classification of brain tumours. The tool improves diagnostic precision of standard methods, and is made available online for broad accessibility. The results illustrate the potential applications of molecular diagnosis tools.
AbstractList	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. 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. An online approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups has been developed to help to improve current diagnostic standards. Classifying tumour types for better diagnoses Precise cancer diagnoses are essential to ensure the best treatment plans for patients, but standardization of the diagnostic process has been challenging. The authors present a comprehensive approach for DNA-methylation-based classification of brain tumours. The tool improves diagnostic precision of standard methods, and is made available online for broad accessibility. The results illustrate the potential applications of molecular diagnosis tools. Accurate pathological diagnosis is crucial for optimal management of cancer patients. For the ~100 known central nervous system (CNS) tumour entities, 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. We herein present the development of a comprehensive approach for DNA methylation-based CNS tumour classification across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that availability of this method may have substantial impact on diagnostic precision compared with 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 (www.molecularneuropathology.org) requiring no 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. 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.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. 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 challengingwith 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.
Audience	Academic
Author	Bendszus, Martin Lechner, Matt Monoranu, Camelia-Maria Schick, Matthias Ellison, David W. Brandner, Sebastian Schweizer, Leonille Collins, Vincent Peter Ketter, Ralf Kulozik, Andreas Karajannis, Matthias A. Koelsche, Christian Korshunov, Andrey Dohmen, Hildegard Hewer, Ekkehard Westphal, Manfred Preusser, Matthias Pietsch, Torsten Hench, Jürgen Coras, Roland Kratz, Annekathrin Hasselblatt, Martin Sill, Martin Seiz-Rosenhagen, Marcel Koch, Arend Unterberg, Andreas Hänggi, Daniel Hartmann, Christian von Deimling, Andreas Taylor, Michael D. Jacques, Thomas S. Beschorner, Rudi Huang, Annie Jaunmuktane, Zane Blümcke, Ingmar Scheurlen, Wolfram Fischer, Roger Farrell, Michael Lindenberg, Kerstin Rodriguez, Fausto J. Geisenberger, Christoph Brehmer, Stefanie Hans, Volkmar Rozsnoki, Stephanie Benner, Axel Wick, Wolfgang Temming, Petra Pohl, Ute Staszewski, Ori Wani, Khalida Mühleisen, Helmut Perry, Arie Gnekow, Astrid Schramm, Johannes Huang, Kristin Schittenhelm, Jens Gajjar, Amar Aronica, Eleonora Weller, Michael Müller, Hermann L. Keohane, Catherine K
AuthorAffiliation	50 University College London Cancer Institute and University College London Hospitals, London, United Kingdom 56 Département de Pathologie et Neuropathologie, Hôpital Neurologique, Hospices Civils de Lyon, Lyon, France 63 Telethon Kids Institute, University of Western Australia, PO Box 855, Perth, Western Australia 6872, Australia 49 Department of Pathology, Odense University Hospital, Department of Clinical Research, University of Southern Denmark, Odense, Denmark 13 Institute of Neurology (Edinger Institute), Goethe-University Frankfurt and German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, Frankfurt am Main, German Cancer Research Center (DKFZ) Heidelberg, Germany 16 Institute of Pathology, University of Bern, Bern, Switzerland 73 Division of Molecular Pathology, Institute of Cancer Research, London, UK 57 Department of Neuropathology, Cork University Hospital, Cork, Ireland 1 Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany 96 Department of Neuro
AuthorAffiliation_xml	– name: 6 Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany – name: 64 School of Paediatrics and Child Health, University of Western Australia, GPO Box D184, Perth, Western Australia 6840, Australia – name: 65 Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany – name: 58 Department of Pathology, Ludwigsburg Hospital, Ludwigsburg, Germany – name: 75 Medical Faculty, University of Bonn Medical School, Bonn, Germany – name: 97 Department of Pathology, University of Toronto, Toronto, Ontario, Canada – name: 79 Department of Pathology, Princess Máxima Center for Pediatric Oncology and University Medical Center Utrecht, Utrecht, the Netherlands, and Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands – name: 74 Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health and 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University of Toronto, Toronto, Canada – name: 30 Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences), Uppsalalaan 8, 3584 CT Utrecht, Netherlands – name: 47 Children’s Cancer Centre, Royal Children’s Hospital; Murdoch Children’s Research Institute; Department of Pediatrics, University of Melbourne; Melbourne, Australia – name: 3 Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neuropathology – name: 80 Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland – name: 72 Department of Pathology, University of California San Francisco, San Francisco, CA, USA – name: 23 Eye Cancer Research Group, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany – name: 62 Department of Pediatric Oncology and Haematology, Princess Margaret Hospital for Children, GPO Box D184, Perth, Western Australia 6840, Australia – name: 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Hamburg, Germany – name: 25 Department of (Neuro)Pathology, Academic Medisch Centrum (AMC) and Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam; Stichting Epilepsie Instellingen Nederland (SEIN), The Netherlands – name: 44 Institut für Neuropathologie, Evangelisches Krankenhaus Bielefeld gGmbH, Bielefeld, Germany – name: 12 Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, Munich, Germany – name: 81 Department of Pathology, Division of Molecular Histopathology, University of Cambridge, Cambridge, UK – name: 35 Department of Biomedicine, University of Bergen, Bergen, Norway – name: 70 Department of Pediatric Hematology/Oncology, University of Bonn Medical Center, Bonn, Germany – name: 46 Institute of Neuropathology, University Hospital Münster, Münster, Germany – name: 2 Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany – name: 24 CCU 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Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada – name: 18 Institute of Pathology and Neuropathology, Department of Neuropathology, University Hospital Tübingen, Tübingen, Germany – name: 41 Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany – name: 68 Department for Pediatric Hematology and Oncology, University Hospital Hamburg-Eppendorf, Hamburg, Germany – name: 11 Department of Oncology and Hematology with Sections Bone Marrow Transplant and Pneumology, Hubertus Wald Tumorzentrum / University Cancer Center Hamburg, University Medical Center Hamburg, Hamburg, Germany – name: 28 Cnopf’sche Kinderklinik Nuremberg, Nuremberg, Germany – name: 55 Cluster of Excellence, NeuroCure, and Berlin Institute of Health (BIH), Berlin, Germany – name: 59 Department of Neuropathology, Leipzig University, Leipzig, Germany – name: 1 Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany – name: 15 Neuropathological 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Essen, Essen, Germany – name: 16 Institute of Pathology, University of Bern, Bern, Switzerland – name: 27 Department of Neuropathology, University Hospital Zurich, Zurich, Switzerland – name: 40 NYU Langone Medical Center, New York, NY, USA – name: 14 Institute of Neuropathology, University of Giessen, Giessen, Germany – name: 71 Department of Neuropathology, Insitute of Pathology, Comprehensive Cancer Center (CCC) Mainfranken, University of Würzburg, Würzburg, Germany – name: 20 Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA – name: 21 Department of Neuropathology, Centre Hospitalier Sainte Anne, Paris, France
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– sequence: 48 givenname: Fausto J. surname: Rodriguez fullname: Rodriguez, Fausto J. organization: Division of Neuropathology of the Johns Hopkins University School of Medicine – sequence: 49 givenname: Albert surname: Becker fullname: Becker, Albert organization: Department of Neuropathology, University of Bonn – sequence: 50 givenname: Matthias surname: Preusser fullname: Preusser, Matthias organization: Department of Medicine I, Comprehensive Cancer Center Vienna, CNS Unit (CCC-CNS), Medical University of Vienna – sequence: 51 givenname: Christine surname: Haberler fullname: Haberler, Christine organization: Institute of Neurology, Medical University of Vienna – sequence: 53 givenname: Jane surname: Cryan fullname: Cryan, Jane organization: Department of Neuropathology, Beaumont Hospital – sequence: 54 givenname: Michael surname: Farrell fullname: Farrell, Michael organization: Department of Neuropathology, Beaumont Hospital – sequence: 55 givenname: Martina surname: Deckert fullname: Deckert, Martina organization: Department of Neuropathology, University Hospital of Cologne – sequence: 56 givenname: Jürgen surname: Hench fullname: Hench, Jürgen organization: Department of Neuropathology, Institute of Pathology, Basel University Hospital – sequence: 57 givenname: Stephan surname: Frank fullname: Frank, Stephan organization: Department of Neuropathology, Institute of Pathology, Basel University Hospital – sequence: 58 givenname: Jonathan surname: Serrano fullname: Serrano, Jonathan organization: NYU Langone Medical Center – sequence: 59 givenname: Kasthuri surname: Kannan fullname: Kannan, Kasthuri organization: NYU Langone Medical Center – sequence: 60 givenname: Aristotelis surname: Tsirigos fullname: Tsirigos, Aristotelis organization: NYU Langone Medical Center – sequence: 61 givenname: Wolfgang surname: Brück fullname: Brück, Wolfgang organization: Institute of Neuropathology, University Medical Center Göttingen – sequence: 62 givenname: Silvia surname: Hofer fullname: Hofer, Silvia organization: Division of Oncology, Luzerner Kantonsspital – sequence: 63 givenname: Stefanie surname: Brehmer fullname: Brehmer, Stefanie organization: Department of Neurosurgery, University Medical Center Mannheim, University of Heidelberg – sequence: 64 givenname: Marcel surname: Seiz-Rosenhagen fullname: Seiz-Rosenhagen, Marcel organization: Department of Neurosurgery, University Medical Center Mannheim, University of Heidelberg – sequence: 65 givenname: Daniel surname: Hänggi fullname: Hänggi, Daniel organization: Department of Neurosurgery, University Medical Center Mannheim, University of Heidelberg – sequence: 67 givenname: Stephanie surname: Rozsnoki fullname: Rozsnoki, Stephanie organization: Institute of Neuropathology, University Hospital Münster – sequence: 68 givenname: Jordan R. surname: Hansford fullname: Hansford, Jordan R. organization: Children’s Cancer Centre, Royal Children’s Hospital, University of Melbourne, Melbourne, Murdoch Children’s Research Institute, University of Melbourne, Department of Pediatrics, University of Melbourne – sequence: 69 givenname: Patricia surname: Kohlhof fullname: Kohlhof, Patricia organization: Institute for Pathology, Katharinenhospital Stuttgart – sequence: 70 givenname: Bjarne W. surname: Kristensen fullname: Kristensen, Bjarne W. organization: Department of Pathology, Department of Clinical Research, Odense University Hospital, University of Southern Denmark – sequence: 71 givenname: Matt surname: Lechner fullname: Lechner, Matt organization: University College London Cancer Institute and University College London Hospitals – sequence: 72 givenname: Beatriz surname: Lopes fullname: Lopes, Beatriz organization: Department of Pathology, University of Virginia – sequence: 73 givenname: Christian surname: Mawrin fullname: Mawrin, Christian organization: Institute of Neuropathology, Otto-von-Guericke-University – sequence: 74 givenname: Ralf surname: Ketter fullname: Ketter, Ralf organization: Department of Neurosurgery, University Hospital Saarland – sequence: 75 givenname: Andreas surname: Kulozik fullname: Kulozik, Andreas organization: Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ), Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg – sequence: 77 givenname: Frank surname: Heppner fullname: Heppner, Frank organization: Department of Neuropathology, 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) – sequence: 78 givenname: Arend surname: Koch fullname: Koch, Arend organization: Department of Neuropathology, Charité — Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health – sequence: 79 givenname: Anne surname: Jouvet fullname: Jouvet, Anne organization: Département de Pathologie et Neuropathologie, Hôpital Neurologique, Hospices Civils de Lyon – sequence: 80 givenname: Catherine surname: Keohane fullname: Keohane, Catherine organization: Department of Neuropathology, Cork University Hospital – sequence: 81 givenname: Helmut surname: Mühleisen fullname: Mühleisen, Helmut organization: Department of Pathology, Ludwigsburg Hospital – sequence: 82 givenname: Wolf surname: Mueller fullname: Mueller, Wolf organization: Department of Neuropathology, Leipzig University – sequence: 88 givenname: Pablo Hernáiz surname: Driever fullname: Driever, Pablo Hernáiz organization: Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin – sequence: 89 givenname: Christof M. surname: Kramm fullname: Kramm, Christof M. organization: Division of Pediatric Hematology and Oncology, University Medical Center Göttingen – sequence: 90 givenname: Hermann L. surname: Müller fullname: Müller, Hermann L. organization: Department of Pediatrics and Pediatric Hematology/Oncology, Klinikum Oldenburg AöR, Medical Campus University Oldenburg – sequence: 91 givenname: Stefan surname: Rutkowski fullname: Rutkowski, Stefan organization: Department for Pediatric Hematology and Oncology, University Hospital Hamburg-Eppendorf – sequence: 93 givenname: Michael C. surname: Frühwald fullname: Frühwald, Michael C. organization: Children’s Hospital Augsburg, Swabian Children’s Cancer Centre – sequence: 94 givenname: Astrid surname: Gnekow fullname: Gnekow, Astrid organization: Children’s Hospital Augsburg, Swabian Children’s Cancer Centre – sequence: 95 givenname: Gudrun surname: Fleischhack fullname: Fleischhack, Gudrun organization: Pediatrics III, Pediatric Oncology and Hematology, University Hospital Essen – sequence: 97 givenname: Gabriele surname: Calaminus fullname: Calaminus, Gabriele organization: Department of Pediatric Hematology/Oncology, University of Bonn Medical Center – sequence: 99 givenname: Arie surname: Perry fullname: Perry, Arie organization: Department of Pathology, University of California San Francisco – sequence: 100 givenname: Chris surname: Jones fullname: Jones, Chris organization: Division of Molecular Pathology, Institute of Cancer Research – sequence: 101 givenname: Thomas S. surname: Jacques fullname: Jacques, Thomas S. organization: UCL Great Ormond Street Institute of Child Health and Histopathology Department, Developmental Biology and Cancer Programme, Great Ormond Street Hospital for Children NHS Foundation Trust – sequence: 102 givenname: Bernhard surname: Radlwimmer fullname: Radlwimmer, Bernhard organization: Division of Molecular Genetics, German Cancer Research Center (DKFZ) – sequence: 103 givenname: Marco surname: Gessi fullname: Gessi, Marco organization: Department of Neuropathology, University of Bonn – sequence: 104 givenname: Torsten surname: Pietsch fullname: Pietsch, Torsten organization: Department of Neuropathology, University of Bonn – sequence: 105 givenname: Johannes surname: Schramm fullname: Schramm, Johannes organization: Medical Faculty, University of Bonn Medical School – sequence: 106 givenname: Gabriele surname: Schackert fullname: Schackert, Gabriele organization: Department of Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden – sequence: 107 givenname: Manfred surname: Westphal fullname: Westphal, Manfred organization: Department of Neurosurgery, University Hospital Hamburg-Eppendorf – sequence: 108 givenname: Guido surname: Reifenberger fullname: Reifenberger, Guido organization: Department of Neuropathology, Heinrich Heine University Düsseldorf, German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, German Cancer Research Center (DKFZ) – sequence: 109 givenname: Pieter surname: Wesseling fullname: Wesseling, Pieter organization: Department of Pathology, Princess Máxima Center for Pediatric Oncology and University Medical Center Utrecht, Department of Pathology, VU University Medical Center – sequence: 110 givenname: Michael surname: Weller fullname: Weller, Michael organization: Department of Neurology, University Hospital and University of Zurich – sequence: 113 givenname: Martin surname: Bendszus fullname: Bendszus, Martin organization: Department of Neuroradiology, Heidelberg University Hospital – sequence: 115 givenname: Annie surname: Huang fullname: Huang, Annie organization: Department of Pediatrics, Laboratory Medicine and Pathobiology, University of Toronto – sequence: 116 givenname: Nada surname: Jabado fullname: Jabado, Nada organization: Division of Hematology/Oncology, McGill University – sequence: 117 givenname: Paul A. surname: Northcott fullname: Northcott, Paul A. organization: Department of Developmental Neurobiology, St Jude Children’s Research Hospital – sequence: 118 givenname: Werner surname: Paulus fullname: Paulus, Werner organization: Institute of Neuropathology, University Hospital Münster – sequence: 119 givenname: Amar surname: Gajjar fullname: Gajjar, Amar organization: Department of Oncology, St Jude Children’s Research Hospital – sequence: 121 givenname: Michael D. surname: Taylor fullname: Taylor, Michael D. organization: Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumor Research Centre, Hospital for Sick Children, University of Toronto – sequence: 123 givenname: Marina surname: Ryzhova fullname: Ryzhova, Marina organization: NN Burdenko Neurosurgical Institute – sequence: 124 givenname: Michael surname: Platten fullname: Platten, Michael organization: Department of Neurology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University – sequence: 125 givenname: Andreas surname: Unterberg fullname: Unterberg, Andreas organization: Department of Neurosurgery, Heidelberg University Hospital – sequence: 126 givenname: Wolfgang surname: Wick fullname: Wick, Wolfgang organization: Department of Neurology, Heidelberg University Hospital – sequence: 129 givenname: Till surname: Acker fullname: Acker, Till organization: Institute of Neuropathology, University of Giessen – sequence: 130 givenname: Christian surname: Hartmann fullname: Hartmann, Christian organization: Department of Neuropathology, Hannover Medical School (MHH) – sequence: 131 givenname: Kenneth surname: Aldape fullname: Aldape, Kenneth organization: Department of Pathology, University of Toronto – sequence: 133 givenname: Rolf surname: Buslei fullname: Buslei, Rolf organization: Neuropathological Institute, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, Section Neuropathology, Institute of Pathology, Sozialstiftung Bamberg, Klinikum am Bruderwald – sequence: 134 givenname: Peter surname: Lichter fullname: Lichter, Peter organization: Division of Molecular Genetics, German Cancer Research Center (DKFZ) – sequence: 135 givenname: Marcel surname: Kool fullname: Kool, Marcel organization: Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ), Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) – sequence: 136 givenname: Christel surname: Herold-Mende fullname: Herold-Mende, Christel organization: Department of Neurosurgery, Heidelberg University Hospital – sequence: 137 givenname: David W. surname: Ellison fullname: Ellison, David W. organization: Department of Pathology, St Jude Children’s Research Hospital – sequence: 138 givenname: Martin surname: Hasselblatt fullname: Hasselblatt, Martin organization: Institute of Neuropathology, University Hospital Münster – sequence: 139 givenname: Matija surname: Snuderl fullname: Snuderl, Matija organization: Division of Neuropathology, Department of Pathology, NYU Langone Medical Center – sequence: 141 givenname: Andrey surname: Korshunov fullname: Korshunov, Andrey organization: Department of Neuropathology, University Hospital Heidelberg, Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) – sequence: 143 givenname: Stefan M. surname: Pfister fullname: Pfister, Stefan M. email: s.pfister@dkfz.de organization: Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ), Division of Pediatric Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg
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R News 2/3, 18–22 (2002) KimKISimonROverfitting, generalization, and MSE in class probability estimation with high-dimensional dataBiom. J.201456256269324968110.1002/bimj.201300083 KoelscheCMelanotic tumors of the nervous system are characterized by distinct mutational, chromosomal and epigenomic profilesBrain Pathol.2015252022081:CAS:528:DC%2BC2MXivVejsbs%3D10.1111/bpa.12228 HeimSPapillary Tumor of the pineal region: a distinct molecular entityBrain Pathol.2016261992051:CAS:528:DC%2BC28Xks1Oltro%3D10.1111/bpa.12282 The Cancer Genome Atlas Research Network. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N. Engl. J. Med.372, 2481–2498 (2015) Boström, H. Calibrating Random Forests. In Proc. 7th International Conference on Machine Learning and Applications 121–126 (ICMLA, 2008) CarterSLAbsolute quantification of somatic DNA alterations in human cancerNat. 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Snippet	Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous... Accurate pathological diagnosis is crucial for optimal management of cancer patients. For the ~100 known central nervous system (CNS) tumour entities,...
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SubjectTerms	13/56 45/61 631/114/1386 631/114/2407 631/67/1922 631/67/69 Adolescent Adult Aged Aged, 80 and over Bioinformatics Brain cancer Cancer Cancer diagnosis Central nervous system Central Nervous System Neoplasms - classification Central Nervous System Neoplasms - diagnosis Central Nervous System Neoplasms - genetics Central Nervous System Neoplasms - pathology Child Child, Preschool Classification Classifiers Clinical trials Cohort Studies Data processing Deoxyribonucleic acid Diagnosis Diagnostic software Diagnostic systems DNA DNA Methylation DNA sequencing Female Gene expression Generalized linear models Genetic aspects Genomes Humanities and Social Sciences Humans Identification and classification Infant Learning algorithms Machine learning Male Medical examination Methods Methylation Middle Aged multidisciplinary Nervous system Observations Probability Reproducibility of Results Science Standardization Tumors Unsupervised Machine Learning Young Adult
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Title	DNA methylation-based classification of central nervous system tumours
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