DNA methylation-based classification of central nervous system tumours

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 Wefers, Kristin Huang, Kristian W Pajtler, Leonille Schweizer, Damian Stichel, Adriana Olar, Nils W Engel, Kerstin Lindenberg, Patrick N Harter & 123 others Anne K Braczynski, Karl H Plate, Hildegard Dohmen, Boyan K Garvalov, Roland Coras, Annett Hölsken, Ekkehard Hewer, Melanie Bewerunge-Hudler, Matthias Schick, Roger Fischer, Rudi Beschorner, Jens Schittenhelm, Ori Staszewski, Khalida Wani, Pascale Varlet, Melanie Pages, Petra Temming, Dietmar Lohmann, Florian Selt, Hendrik Witt, Till Milde, Olaf Witt, Eleonora Aronica, Felice Giangaspero, Elisabeth Rushing, Wolfram Scheurlen, Christoph Geisenberger, Fausto J Rodriguez, Albert Becker, Matthias Preusser, Christine Haberler, Rolf Bjerkvig, Jane Cryan, Michael Farrell, Martina Deckert, Jürgen Hench, Stephan Frank, Jonathan Serrano, Kasthuri Kannan, Aristotelis Tsirigos, Wolfgang Brück, Silvia Hofer, Stefanie Brehmer, Marcel Seiz-Rosenhagen, Daniel Hänggi, Volkmar Hans, Stephanie Rozsnoki, Jordan R Hansford, Patricia Kohlhof, Bjarne W Kristensen, Matt Lechner, Beatriz Lopes, Christian Mawrin, Ralf Ketter, Andreas Kulozik, Ziad Khatib, Frank Heppner, Arend Koch, Anne Jouvet, Catherine Keohane, Helmut Mühleisen, Wolf Mueller, Ute Pohl, Marco Prinz, Axel Benner, Marc Zapatka, Nicholas G Gottardo, Pablo Hernáiz Driever, Christof M Kramm, Hermann L Müller, Stefan Rutkowski, Katja von Hoff, Michael C Frühwald, Astrid Gnekow, Gudrun Fleischhack, Stephan Tippelt, Gabriele Calaminus, Camelia-Maria Monoranu, Arie Perry, Chris Jones, Thomas S Jacques, Bernhard Radlwimmer, Marco Gessi, Torsten Pietsch, Johannes Schramm, Gabriele Schackert, Manfred Westphal, Guido Reifenberger, Pieter Wesseling, Michael Weller, Vincent Peter Collins, Ingmar Blümcke, Martin Bendszus, Jürgen Debus, Annie Huang, Nada Jabado, Paul A Northcott, Werner Paulus, Amar Gajjar, Giles W Robinson, Michael D Taylor, Zane Jaunmuktane, Marina Ryzhova, Michael Platten, Andreas Unterberg, Wolfgang Wick, Matthias A Karajannis, Michel Mittelbronn, Till Acker, Christian Hartmann, Kenneth Aldape, Ulrich Schüller, Rolf Buslei, Peter Lichter, Marcel Kool, Christel Herold-Mende, David W Ellison, Martin Hasselblatt, Matija Snuderl, Sebastian Brandner, Andrey Korshunov, Andreas von Deimling, Stefan M Pfister

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)469-474
Number of pages6
JournalNature
Volume555
Issue number7697
DOIs
Publication statusPublished - Mar 22 2018

Fingerprint

Central Nervous System Neoplasms
DNA Methylation
Neoplasms
Observer Variation
Age Groups
Pathology

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Central Nervous System Neoplasms/classification
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Methylation
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Reproducibility of Results
  • Unsupervised Machine Learning
  • Young Adult

Cite this

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

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 journalArticle

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, 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, 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, Brück, W, Hofer, S, Brehmer, S, Seiz-Rosenhagen, M, Hänggi, 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, Mühleisen, H, Mueller, W, Pohl, U, Prinz, M, Benner, A, Zapatka, M, Gottardo, NG, Driever, PH, Kramm, CM, Müller, HL, Rutkowski, S, von Hoff, K, Frühwald, MC, Gnekow, A, Fleischhack, G, Tippelt, S, Calaminus, G, Monoranu, C-M, 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, Schüller, 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, 'DNA methylation-based classification of central nervous system tumours', Nature, vol. 555, no. 7697, pp. 469-474. https://doi.org/10.1038/nature26000
Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D et al. DNA methylation-based classification of central nervous system tumours. Nature. 2018 Mar 22;555(7697):469-474. https://doi.org/10.1038/nature26000
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. / DNA methylation-based classification of central nervous system tumours. In: Nature. 2018 ; Vol. 555, No. 7697. pp. 469-474.
@article{8d443eab6fee40b5b970e0aff11b0454,
title = "DNA methylation-based classification of central nervous system tumours",
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.",
keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Central Nervous System Neoplasms/classification, Child, Child, Preschool, Cohort Studies, DNA Methylation, Female, Humans, Infant, Male, Middle Aged, Reproducibility of Results, Unsupervised Machine Learning, Young Adult",
author = "David Capper and Jones, {David T W} and Martin Sill and Volker Hovestadt and Daniel Schrimpf and Dominik Sturm and Christian Koelsche and Felix Sahm and Lukas Chavez and Reuss, {David E} and Annekathrin Kratz and Wefers, {Annika K} and Kristin Huang and Pajtler, {Kristian W} and Leonille Schweizer and Damian Stichel and Adriana Olar and Engel, {Nils W} and Kerstin Lindenberg and Harter, {Patrick N} and Braczynski, {Anne K} and Plate, {Karl H} and Hildegard Dohmen and Garvalov, {Boyan K} and Roland Coras and Annett H{\"o}lsken and Ekkehard Hewer and Melanie Bewerunge-Hudler and Matthias Schick and Roger Fischer and Rudi Beschorner and Jens Schittenhelm and Ori Staszewski and Khalida Wani and Pascale Varlet and Melanie Pages and Petra Temming and Dietmar Lohmann and Florian Selt and Hendrik Witt and Till Milde and Olaf Witt and Eleonora Aronica and Felice Giangaspero and Elisabeth Rushing and Wolfram Scheurlen and Christoph Geisenberger and Rodriguez, {Fausto J} and Albert Becker and Matthias Preusser and Christine Haberler and Rolf Bjerkvig and Jane Cryan and Michael Farrell and Martina Deckert and J{\"u}rgen Hench and Stephan Frank and Jonathan Serrano and Kasthuri Kannan and Aristotelis Tsirigos and Wolfgang Br{\"u}ck and Silvia Hofer and Stefanie Brehmer and Marcel Seiz-Rosenhagen and Daniel H{\"a}nggi and Volkmar Hans and Stephanie Rozsnoki and Hansford, {Jordan R} and Patricia Kohlhof and Kristensen, {Bjarne W} and Matt Lechner and Beatriz Lopes and Christian Mawrin and Ralf Ketter and Andreas Kulozik and Ziad Khatib and Frank Heppner and Arend Koch and Anne Jouvet and Catherine Keohane and Helmut M{\"u}hleisen and Wolf Mueller and Ute Pohl and Marco Prinz and Axel Benner and Marc Zapatka and Gottardo, {Nicholas G} and Driever, {Pablo Hern{\'a}iz} and Kramm, {Christof M} and M{\"u}ller, {Hermann L} and Stefan Rutkowski and {von Hoff}, Katja and Fr{\"u}hwald, {Michael C} and Astrid Gnekow and Gudrun Fleischhack and Stephan Tippelt and Gabriele Calaminus and Camelia-Maria Monoranu and Arie Perry and Chris Jones and Jacques, {Thomas S} and Bernhard Radlwimmer and Marco Gessi and Torsten Pietsch and Johannes Schramm and Gabriele Schackert and Manfred Westphal and Guido Reifenberger and Pieter Wesseling and Michael Weller and Collins, {Vincent Peter} and Ingmar Bl{\"u}mcke and Martin Bendszus and J{\"u}rgen Debus and Annie Huang and Nada Jabado and Northcott, {Paul A} and Werner Paulus and Amar Gajjar and Robinson, {Giles W} and Taylor, {Michael D} and Zane Jaunmuktane and Marina Ryzhova and Michael Platten and Andreas Unterberg and Wolfgang Wick and Karajannis, {Matthias A} and Michel Mittelbronn and Till Acker and Christian Hartmann and Kenneth Aldape and Ulrich Sch{\"u}ller and Rolf Buslei and Peter Lichter and Marcel Kool and Christel Herold-Mende and Ellison, {David W} and Martin Hasselblatt and Matija Snuderl and Sebastian Brandner and Andrey Korshunov and {von Deimling}, Andreas and Pfister, {Stefan M}",
year = "2018",
month = "3",
day = "22",
doi = "10.1038/nature26000",
language = "English",
volume = "555",
pages = "469--474",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7697",

}

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

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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Central Nervous System Neoplasms/classification

KW - Child

KW - Child, Preschool

KW - Cohort Studies

KW - DNA Methylation

KW - Female

KW - Humans

KW - Infant

KW - Male

KW - Middle Aged

KW - Reproducibility of Results

KW - Unsupervised Machine Learning

KW - Young Adult

U2 - 10.1038/nature26000

DO - 10.1038/nature26000

M3 - Article

VL - 555

SP - 469

EP - 474

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7697

ER -