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.
Original language | English (US) |
---|---|
Pages (from-to) | 469-474 |
Number of pages | 6 |
Journal | Nature |
Volume | 555 |
Issue number | 7697 |
DOIs | |
State | Published - Mar 22 2018 |
ASJC Scopus subject areas
- General
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DNA methylation-based classification of central nervous system tumours. / 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.
In: Nature, Vol. 555, No. 7697, 22.03.2018, p. 469-474.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - DNA methylation-based classification of central nervous system tumours
AU - Capper, David
AU - Jones, David T.W.
AU - Sill, Martin
AU - Hovestadt, Volker
AU - Schrimpf, Daniel
AU - Sturm, Dominik
AU - Koelsche, Christian
AU - Sahm, Felix
AU - Chavez, Lukas
AU - Reuss, David E.
AU - Kratz, Annekathrin
AU - Wefers, Annika K.
AU - Huang, Kristin
AU - Pajtler, Kristian W.
AU - Schweizer, Leonille
AU - Stichel, Damian
AU - Olar, Adriana
AU - Engel, Nils W.
AU - Lindenberg, Kerstin
AU - Harter, Patrick N.
AU - Braczynski, Anne K.
AU - Plate, Karl H.
AU - Dohmen, Hildegard
AU - Garvalov, Boyan K.
AU - Coras, Roland
AU - Hölsken, Annett
AU - Hewer, Ekkehard
AU - Bewerunge-Hudler, Melanie
AU - Schick, Matthias
AU - Fischer, Roger
AU - Beschorner, Rudi
AU - Schittenhelm, Jens
AU - Staszewski, Ori
AU - Wani, Khalida
AU - Varlet, Pascale
AU - Pages, Melanie
AU - Temming, Petra
AU - Lohmann, Dietmar
AU - Selt, Florian
AU - Witt, Hendrik
AU - Milde, Till
AU - Witt, Olaf
AU - Aronica, Eleonora
AU - Giangaspero, Felice
AU - Rushing, Elisabeth
AU - Scheurlen, Wolfram
AU - Geisenberger, Christoph
AU - Rodriguez, Fausto J.
AU - Becker, Albert
AU - Preusser, Matthias
AU - Haberler, Christine
AU - Bjerkvig, Rolf
AU - Cryan, Jane
AU - Farrell, Michael
AU - Deckert, Martina
AU - Hench, Jürgen
AU - Frank, Stephan
AU - Serrano, Jonathan
AU - Kannan, Kasthuri
AU - Tsirigos, Aristotelis
AU - Brück, Wolfgang
AU - Hofer, Silvia
AU - Brehmer, Stefanie
AU - Seiz-Rosenhagen, Marcel
AU - Hänggi, Daniel
AU - Hans, Volkmar
AU - Rozsnoki, Stephanie
AU - Hansford, Jordan R.
AU - Kohlhof, Patricia
AU - Kristensen, Bjarne W.
AU - Lechner, Matt
AU - Lopes, Beatriz
AU - Mawrin, Christian
AU - Ketter, Ralf
AU - Kulozik, Andreas
AU - Khatib, Ziad
AU - Heppner, Frank
AU - Koch, Arend
AU - Jouvet, Anne
AU - Keohane, Catherine
AU - Mühleisen, Helmut
AU - Mueller, Wolf
AU - Pohl, Ute
AU - Prinz, Marco
AU - Benner, Axel
AU - Zapatka, Marc
AU - Gottardo, Nicholas G.
AU - Driever, Pablo Hernáiz
AU - Kramm, Christof M.
AU - Müller, Hermann L.
AU - Rutkowski, Stefan
AU - Von Hoff, Katja
AU - Frühwald, Michael C.
AU - Gnekow, Astrid
AU - Fleischhack, Gudrun
AU - Tippelt, Stephan
AU - Calaminus, Gabriele
AU - Monoranu, Camelia Maria
AU - Perry, Arie
AU - Jones, Chris
AU - Jacques, Thomas S.
AU - Radlwimmer, Bernhard
AU - Gessi, Marco
AU - Pietsch, Torsten
AU - Schramm, Johannes
AU - Schackert, Gabriele
AU - Westphal, Manfred
AU - Reifenberger, Guido
AU - Wesseling, Pieter
AU - Weller, Michael
AU - Collins, Vincent Peter
AU - Blümcke, Ingmar
AU - Bendszus, Martin
AU - Debus, Jürgen
AU - Huang, Annie
AU - Jabado, Nada
AU - Northcott, Paul A.
AU - Paulus, Werner
AU - Gajjar, Amar
AU - Robinson, Giles W.
AU - Taylor, Michael D.
AU - Jaunmuktane, Zane
AU - Ryzhova, Marina
AU - Platten, Michael
AU - Unterberg, Andreas
AU - Wick, Wolfgang
AU - Karajannis, Matthias A.
AU - Mittelbronn, Michel
AU - Acker, Till
AU - Hartmann, Christian
AU - Aldape, Kenneth
AU - Schüller, Ulrich
AU - Buslei, Rolf
AU - Lichter, Peter
AU - Kool, Marcel
AU - Herold-Mende, Christel
AU - Ellison, David W.
AU - Hasselblatt, Martin
AU - Snuderl, Matija
AU - Brandner, Sebastian
AU - Korshunov, Andrey
AU - Von Deimling, Andreas
AU - Pfister, Stefan M.
N1 - Publisher Copyright: © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
PY - 2018/3/22
Y1 - 2018/3/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85044262739&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044262739&partnerID=8YFLogxK
U2 - 10.1038/nature26000
DO - 10.1038/nature26000
M3 - Article
C2 - 29539639
AN - SCOPUS:85044262739
VL - 555
SP - 469
EP - 474
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7697
ER -