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DNA methylation-based classification of central nervous system tumours

Open access
Capper, David, Jones, David T. W., Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E., Kratz, Annekathrin, Wefers, Annika K., Huang, Kristin, Pajtler, Kristian W., Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Coras, Roland, Hölsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, 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, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Mühleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernáiz, Kramm, Christof M., Müller, Hermann L., Rutkowski, Stefan, von Hoff, Katja, Frühwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia-Maria, 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, Collins, Vincent Peter, Blümcke, Ingmar, Bendszus, Martin, Debus, Jürgen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schüller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, von Deimling, Andreas, Pfister, Stefan M.·2018·Nature
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.

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Metadata

Authors
Capper, D., Jones, D. T. W., Sill, M., Hovestadt, V., Schrimpf, D., Sturm, D., Koelsche, C., Sahm, F., Chavez, L., Reuss, D. E., Kratz, A., Wefers, A. K., Huang, K., Pajtler, K. W., Schweizer, L., Stichel, D., Olar, A., Engel, N. W., Lindenberg, K., Harter, P. N., Braczynski, A. K., Plate, K. H., Dohmen, H., Garvalov, B. K., Coras, R., Hölsken, 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, F. J., Becker, A., Preusser, M., Haberler, C., Bjerkvig, R., Cryan, J., Farrell, M., Deckert, M., Hench, J., Frank, S., Serrano, J., Kannan, K., Tsirigos, A., Brück, W., Hofer, S., Brehmer, S., Seiz-Rosenhagen, M., Hänggi, D., Hans, V., Rozsnoki, S., Hansford, J. R., Kohlhof, P., Kristensen, B. W., Lechner, M., Lopes, B., Mawrin, C., Ketter, R., Kulozik, A., Khatib, Z., Heppner, F., Koch, A., Jouvet, A., Keohane, C., Mühleisen, H., Mueller, W., Pohl, U., Prinz, M., Benner, A., Zapatka, M., Gottardo, N. G., Driever, P. H., Kramm, C. M., Müller, H. L., Rutkowski, S., von Hoff, K., Frühwald, M. C., Gnekow, A., Fleischhack, G., Tippelt, S., Calaminus, G., Monoranu, C.-M., Perry, A., Jones, C., Jacques, T. S., Radlwimmer, B., Gessi, M., Pietsch, T., Schramm, J., Schackert, G., Westphal, M., Reifenberger, G., Wesseling, P., Weller, M., Collins, V. P., Blümcke, I., Bendszus, M., Debus, J., Huang, A., Jabado, N., Northcott, P. A., Paulus, W., Gajjar, A., Robinson, G. W., Taylor, M. D., Jaunmuktane, Z., Ryzhova, M., Platten, M., Unterberg, A., Wick, W., Karajannis, M. A., Mittelbronn, M., Acker, T., Hartmann, C., Aldape, K., Schüller, U., Buslei, R., Lichter, P., Kool, M., Herold-Mende, C., Ellison, D. W., Hasselblatt, M., Snuderl, M., Brandner, S., Korshunov, A., von Deimling, A., & Pfister, S. M.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2018-03-14
Volume
555
Issue
7697
Pages
469-474
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature26000
OpenAlex
W2787816121
Cited by
3,033
References
8
FWCI
133.84
Type
journal article
Language
en
Open access
green
Licence

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CoChat. (2026). Citation check: DNA methylation-based classification of central nervous system tumours. https://app.cochat.ai/papers/10.1038/nature26000
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Capper, D., Jones, D. T. W., Sill, M., Hovestadt, V., Schrimpf, D., Sturm, D., Koelsche, C., Sahm, F., Chavez, L., Reuss, D. E., Kratz, A., Wefers, A. K., Huang, K., Pajtler, K. W., Schweizer, L., Stichel, D., Olar, A., Engel, N. W., Lindenberg, K., . . . Pfister, S. M. (2018). DNA methylation-based classification of central nervous system tumours. Nature. https://doi.org/10.1038/nature26000

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