DNA methylation-based classification of central nervous system tumours

Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D, Koelsche C, Sahm F, Chavez L, Reuss DE, Kratz A, Wefers AK, Huang K, Pajtler KW, Schweizer L, Stichel D, Olar A, Engel NW, Lindenberg K, Harter PN, Braczynski AK, Plate KH, Dohmen H, Garvalov BK, Coras R, Hoelsken A, Hewer E, Bewerunge-Hudler M, Schick M, Fischer R, Beschorner R, Schittenhelm J, Staszewski O, Wani K, Varlet P, Pages M, Temming P, Lohmann D, Selt F, Witt H, Milde T, Witt O, Aronica E, Giangaspero F, Rushing E, Scheurlen W, Geisenberger C, Rodriguez FJ, Becker A, Preusser M, Haberler C, Bjerkvig R, Cryan J, Farrell M, Deckert M, Hench J, Frank S, Serrano J, Kannan K, Tsirigos A, Brueck W, Hofer S, Brehmer S, Seiz-Rosenhagen M, Haenggi D, Hans V, Rozsnoki S, Hansford JR, Kohlhof P, Kristensen BW, Lechner M, Lopes B, Mawrin C, Ketter R, Kulozik A, Khatib Z, Heppner F, Koch A, Jouvet A, Keohane C, Muehleisen H, Mueller W, Pohl U, Prinz M, Benner A, Zapatka M, Gottardo NG, Driever PH, Kramm CM, Mueller HL, Rutkowski S, Von Hoff K, Fruehwald MC, Gnekow A, Fleischhack G, Tippelt S, Calaminus G, Monoranu CM, Perry A, Jones C, Jacques TS, Radlwimmer B, Gessi M, Pietsch T, Schramm J, Schackert G, Westphal M, Reifenberger G, Wesseling P, Weller M, Collins VP, Blümcke I, Bendszus M, Debus J, Huang A, Jabado N, Northcott PA, Paulus W, Gajjar A, Robinson GW, Taylor MD, Jaunmuktane Z, Ryzhova M, Platten M, Unterberg A, Wick W, Karajannis MA, Mittelbronn M, Acker T, Hartmann C, Aldape K, Schueller U, Buslei R, Lichter P, Kool M, Herold-Mende C, Ellison DW, Hasselblatt M, Snuderl M, Brandner S, Korshunov A, Von Deimling A, Pfister SM (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 555

Pages Range: 469-474

Journal Issue: 7697

DOI: 10.1038/nature26000

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.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Heidelberg Germany (DE) Hopp-Kindertumorzentrum Heidelberg - KiTZ Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Otto-von-Guericke-Universität Magdeburg Germany (DE) Universitätsklinikum des Saarlandes (UKS) Germany (DE) The University of Melbourne Australia (AU) Medizinische Universität Wien Austria (AT) Universität Duisburg-Essen (UDE) Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Katharinenhospital Stuttgart Germany (DE) Universitätsklinikum Tübingen Germany (DE) Università degli studi "La Sapienza" Italy (IT) Universitätsklinikum Essen Germany (DE) Centre hospitalier Sainte-Anne France (FR) Goethe-Universität Frankfurt am Main Germany (DE) Universität Bern Switzerland (CH) University of Amsterdam Netherlands (NL) Universitätsspital Zürich (USZ) Switzerland (CH) University College London (UCL) United Kingdom (GB) Universitätsspital Basel Switzerland (CH) University of Bergen / Universitetet i Bergen Norway (NO) Medical University of South Carolina (MUSC) United States (USA) (US) Universitätsklinikum Köln Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) New York University (NYU) United States (USA) (US) Ruprecht-Karls-Universität Heidelberg Germany (DE) University of Toronto Canada (CA) Rheinische Friedrich-Wilhelms-Universität Bonn Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Queen's Hospital United Kingdom (GB) Nikolay Nilovich Burdenko Neurosurgery Institute / Центр нейрохирургии имени академика Н. Н. Бурденко Russian Federation (RU) Universitätsklinikum Augsburg Germany (DE) Hospices Civils de Lyon (CHU) France (FR) Universität Leipzig Germany (DE) Princess Máxima Center Netherlands (NL) University of California San Francisco (UCSF) United States (USA) (US) Great Ormond Street Hospital (GOSH) United Kingdom (GB) University of Cambridge United Kingdom (GB) Carl von Ossietzky Universität Oldenburg Germany (DE) Universitätsklinikum Göttingen Germany (DE) Technische Universität Dresden Germany (DE) South Infirmary Victoria University Hospital Ireland (IE) St. Jude Children’s Research Hospital United States (USA) (US) Universitätsklinikum Münster Germany (DE) McGill University Canada (CA) The Institute of Cancer Research (ICR) United Kingdom (GB) Julius-Maximilians-Universität Würzburg Germany (DE) Beaumont Hospital Ireland (IE) Albert-Ludwigs-Universität Freiburg Germany (DE) University of Southern Denmark / Syddansk Universitet Denmark (DK) Diakonie Neuendettelsau Germany (DE) Justus-Liebig-Universität Gießen Germany (DE) University of Virginia (UVA) United States (USA) (US) Klinikum Ludwigsburg Germany (DE) Perth Children's Hospital Australia (AU) Evangelisches Krankenhaus Bielefeld Germany (DE) Heinrich-Heine-Universität Düsseldorf Germany (DE) Johns Hopkins University (JHU) United States (USA) (US) Ludwig-Maximilians-Universität (LMU) Germany (DE) Nicklaus Children's Hospital United States (USA) (US) University of Texas MD Anderson Cancer Center United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) Luzerner Kantonsspital (LUKS) Switzerland (CH)

How to cite

APA:

Capper, D., Jones, D.T.W., Sill, M., Hovestadt, V., Schrimpf, D., Sturm, D.,... Pfister, S.M. (2018). DNA methylation-based classification of central nervous system tumours. Nature, 555(7697), 469-474. https://doi.org/10.1038/nature26000

MLA:

Capper, David, et al. "DNA methylation-based classification of central nervous system tumours." Nature 555.7697 (2018): 469-474.

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