Sarcoma classification by DNA methylation profiling

Christian Koelsche, Daniel Schrimpf, Damian Stichel, Martin Sill, Felix Sahm, David E. Reuss, Mirjam Blattner, Barbara Worst, Christoph E. Heilig, Katja Beck, Peter Horak, Simon Kreutzfeldt, Elke Paff, Sebastian Stark, Pascal Johann, Florian Selt, Jonas Ecker, Dominik Sturm, Kristian W. Pajtler, Annekathrin Reinhardt, Annika K. Wefers, Philipp Sievers, Azadeh Ebrahimi, Abigail Suwala, Francisco Fernández-Klett, Belén Casalini, Andrey Korshunov, Volker Hovestadt, Felix K. F. Kommoss, Mark Kriegsmann, Matthias Schick, Melanie Bewerunge-Hudler, Till Milde, Olaf Witt, Andreas E. Kulozik, Marcel Kool, Laura Romero-Pérez, Thomas G. P. Grünewald, Thomas Kirchner, Wolfgang Wick, Michael Platten, Andreas Unterberg, Matthias Uhl, Amir Abdollahi, Jürgen Debus, Burkhard Lehner, Christian Thomas, Martin Hasselblatt, Werner Paulus, Christian Hartmann, Ori Staszewski, Marco Prinz, Jürgen Hench, Stephan Frank, Yvonne M. H. Versleijen-Jonkers, Marije E. Weidema, Thomas Mentzel, Klaus Griewank, Enrique Álava, Juan Díaz Martín, Miguel A. Idoate Gastearena, Kenneth Tou-En Chang, Sharon Yin Yee Low, Adrian Cuevas-Bourdier, Michel Mittelbronn, Martin Mynarek, Stefan Rutkowski, Ulrich Schüller, Viktor F. Mautner, Jens Schittenhelm, Jonathan Serrano, Matija Snuderl, Reinhard Büttner, Thomas Klingebiel, Rolf Buslei, Manfred Gessler, Pieter Wesseling, Winand N. M. Dinjens, Sebastian Brandner, Zane Jaunmuktane, Iben Lyskjær, Peter Schirmacher, Albrecht Stenzinger, Benedikt Brors, Hanno Glimm, Christoph Heining, Oscar M. Tirado, Miguel Sáinz-Jaspeado, Jaume Mora, Javier Alonso, Xavier Garcia Muro, Sebastian Moran, Manel Esteller, Jamal K. Benhamida, Marc Ladanyi, Eva Wardelmann, Cristina Antonescu, Adrienne Flanagan, Uta Dirksen, Peter Hohenberger, Daniel Baumhoer, Wolfgang Hartmann, Christian Vokuhl, Uta Flucke, Iver Petersen, Gunhild Mechtersheimer, David Capper, David T. W. Jones, Stefan Fröhling, Stefan M. Pfister and Andreas Deimling ()
Additional contact information
Christian Koelsche: Institute of Pathology, Heidelberg University Hospital
Daniel Schrimpf: Institute of Pathology, Heidelberg University Hospital
Damian Stichel: German Cancer Research Center (DKFZ)
Martin Sill: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Felix Sahm: Institute of Pathology, Heidelberg University Hospital
David E. Reuss: Institute of Pathology, Heidelberg University Hospital
Mirjam Blattner: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Barbara Worst: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Christoph E. Heilig: National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK)
Katja Beck: National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK)
Peter Horak: National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK)
Simon Kreutzfeldt: National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK)
Elke Paff: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Sebastian Stark: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Pascal Johann: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Florian Selt: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Jonas Ecker: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Dominik Sturm: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Kristian W. Pajtler: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Annekathrin Reinhardt: Institute of Pathology, Heidelberg University Hospital
Annika K. Wefers: Institute of Pathology, Heidelberg University Hospital
Philipp Sievers: Institute of Pathology, Heidelberg University Hospital
Azadeh Ebrahimi: German Cancer Research Center (DKFZ)
Abigail Suwala: Institute of Pathology, Heidelberg University Hospital
Francisco Fernández-Klett: Institute of Pathology, Heidelberg University Hospital
Belén Casalini: German Cancer Research Center (DKFZ)
Andrey Korshunov: Institute of Pathology, Heidelberg University Hospital
Volker Hovestadt: Broad Institute of MIT and Harvard
Felix K. F. Kommoss: Institute of Pathology, Heidelberg University Hospital
Mark Kriegsmann: Institute of Pathology, Heidelberg University Hospital
Matthias Schick: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ)
Melanie Bewerunge-Hudler: German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ)
Till Milde: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Olaf Witt: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Andreas E. Kulozik: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Marcel Kool: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Laura Romero-Pérez: Institute of Pathology, Faculty of Medicine, LMU Munich
Thomas G. P. Grünewald: Institute of Pathology, Faculty of Medicine, LMU Munich
Thomas Kirchner: Institute of Pathology, Faculty of Medicine, LMU Munich
Wolfgang Wick: University Hospital Heidelberg
Michael Platten: Mannheim University Medical Center, University of Heidelberg
Andreas Unterberg: Heidelberg University Hospital
Matthias Uhl: Heidelberg University Hospital
Amir Abdollahi: Heidelberg University Hospital
Jürgen Debus: Heidelberg University Hospital
Burkhard Lehner: Heidelberg University Hospital
Christian Thomas: University Hospital Münster
Martin Hasselblatt: University Hospital Münster
Werner Paulus: University Hospital Münster
Christian Hartmann: Institute of Pathology, Hannover Medical School (MHH)
Ori Staszewski: University of Freiburg
Marco Prinz: University of Freiburg
Jürgen Hench: Basel University Hospital
Stephan Frank: Basel University Hospital
Yvonne M. H. Versleijen-Jonkers: Radboud University Medical Center
Marije E. Weidema: Radboud University Medical Center
Thomas Mentzel: Dermatopathology Bodensee
Klaus Griewank: University Hospital Essen, West German Cancer Center, University Duisburg-Essen
Enrique Álava: Virgen del Rocio University Hospital, CSIC/University of Sevilla/CIBERONC
Juan Díaz Martín: Virgen del Rocio University Hospital, CSIC/University of Sevilla/CIBERONC
Miguel A. Idoate Gastearena: University of Navarra
Kenneth Tou-En Chang: KK Women’s and Children’s Hospital
Sharon Yin Yee Low: National Neuroscience Institute
Adrian Cuevas-Bourdier: Laboratoire National de Santé (LNS)
Michel Mittelbronn: Laboratoire National de Santé (LNS)
Martin Mynarek: University Medical Center Hamburg-Eppendorf
Stefan Rutkowski: University Medical Center Hamburg-Eppendorf
Ulrich Schüller: University Medical Center Hamburg-Eppendorf
Viktor F. Mautner: University Medical Center Hamburg-Eppendorf
Jens Schittenhelm: University Hospital of Tübingen
Jonathan Serrano: New York University School of Medicine
Matija Snuderl: New York University School of Medicine
Reinhard Büttner: Cologne University Hospital
Thomas Klingebiel: University Children’s Hospital
Rolf Buslei: Institute of Pathology, Sozialstiftung Bamberg, Klinikum am Bruderwald
Manfred Gessler: Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Würzburg University
Pieter Wesseling: Princess Máxima Center for Pediatric Oncology
Winand N. M. Dinjens: Erasmus MC Cancer Institute
Sebastian Brandner: University College London
Zane Jaunmuktane: University College London Hospitals NHS Foundation Trust
Iben Lyskjær: University College London
Peter Schirmacher: Institute of Pathology, Heidelberg University Hospital
Albrecht Stenzinger: Institute of Pathology, Heidelberg University Hospital
Benedikt Brors: German Cancer Research Center (DKFZ)
Hanno Glimm: National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ)
Christoph Heining: National Center for Tumor Diseases (NCT) Dresden and German Cancer Research Center (DKFZ)
Oscar M. Tirado: Bellvitge Biomedical Research Institute (IDIBELL), CIBERONC
Miguel Sáinz-Jaspeado: Bellvitge Biomedical Research Institute (IDIBELL), CIBERONC
Jaume Mora: Hospital Sant Joan de Déu
Javier Alonso: Human Genetic Department, Research Institute of Rare Diseases, Instituto de Salud Carlos III (ISCIII)
Xavier Garcia Muro: University of Barcelona
Sebastian Moran: Bellvitge Biomedical Research Institute (IDIBELL)
Manel Esteller: Josep Carreras Leukaemia Research Institute (IJC), Badalona
Jamal K. Benhamida: Memorial Sloan Kettering Cancer Center
Marc Ladanyi: Memorial Sloan Kettering Cancer Center
Eva Wardelmann: University Hospital Münster
Cristina Antonescu: Memorial Sloan Kettering Cancer Center
Adrienne Flanagan: Royal National Orthopaedic Hospital NHS Trust
Uta Dirksen: University Hospital Essen
Peter Hohenberger: University of Heidelberg
Daniel Baumhoer: University Hospital Basel and University of Basel
Wolfgang Hartmann: University Hospital Münster
Christian Vokuhl: University Hospital of Schleswig-Holstein
Uta Flucke: Radboud University Medical Center
Iver Petersen: Institute of Pathology, SRH Poliklinik Gera GmbH
Gunhild Mechtersheimer: Institute of Pathology, Heidelberg University Hospital
David Capper: Charité Universitätsmedizin Berlin
David T. W. Jones: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Stefan Fröhling: National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK)
Stefan M. Pfister: Hopp Children’s Cancer Center Heidelberg (KiTZ)
Andreas Deimling: Institute of Pathology, Heidelberg University Hospital

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20603-4

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DOI: 10.1038/s41467-020-20603-4

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