Sarcoma classification by DNA methylation profiling

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Christian Koelsche - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Daniel Schrimpf - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Damian Stichel - , German Cancer Research Center (DKFZ) (Author)
  • Martin Sill - , Hopp Children's Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ) (Author)
  • Felix Sahm - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • David E. Reuss - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Mirjam Blattner - , Hopp Children's Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ) (Author)
  • Barbara Worst - , Hopp Children's Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Christoph E. Heilig - , German Cancer Research Center (DKFZ) (Author)
  • Katja Beck - , German Cancer Research Center (DKFZ) (Author)
  • Peter Horak - , German Cancer Research Center (DKFZ) (Author)
  • Simon Kreutzfeldt - , German Cancer Research Center (DKFZ) (Author)
  • Elke Paff - , Hopp Children's Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Sebastian Stark - , Hopp Children's Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Pascal Johann - , Hopp Children's Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Florian Selt - , Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Jonas Ecker - , Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Dominik Sturm - , Hopp Children's Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Kristian W. Pajtler - , Hopp Children's Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Annekathrin Reinhardt - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Annika K. Wefers - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Philipp Sievers - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Azadeh Ebrahimi - , German Cancer Research Center (DKFZ) (Author)
  • Abigail Suwala - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Francisco Fernández-Klett - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Belén Casalini - , German Cancer Research Center (DKFZ) (Author)
  • Andrey Korshunov - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Volker Hovestadt - , Broad Institute of Harvard University and MIT, Massachusetts General Hospital (Author)
  • Felix K.F. Kommoss - , Heidelberg University  (Author)
  • Mark Kriegsmann - , Heidelberg University  (Author)
  • Matthias Schick - , German Cancer Research Center (DKFZ) (Author)
  • Melanie Bewerunge-Hudler - , German Cancer Research Center (DKFZ) (Author)
  • Till Milde - , Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Olaf Witt - , Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Andreas E. Kulozik - , Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University  (Author)
  • Marcel Kool - , Hopp Children's Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ) (Author)
  • Laura Romero-Pérez - , Ludwig Maximilian University of Munich (Author)
  • Thomas G.P. Grünewald - , Ludwig Maximilian University of Munich (Author)
  • Thomas Kirchner - , Ludwig Maximilian University of Munich (Author)
  • Wolfgang Wick - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Michael Platten - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)
  • Andreas Unterberg - , Heidelberg University  (Author)
  • Matthias Uhl - , Heidelberg University , OncoRay - National Centre for Radiation Research in Oncology (Author)
  • Amir Abdollahi - , Heidelberg University , OncoRay - National Centre for Radiation Research in Oncology, German Cancer Research Center (DKFZ) (Author)
  • Jürgen Debus - , Heidelberg University , OncoRay - National Centre for Radiation Research in Oncology, German Cancer Research Center (DKFZ) (Author)
  • Burkhard Lehner - , Heidelberg University  (Author)
  • Christian Thomas - , University of Münster (Author)
  • Martin Hasselblatt - , University of Münster (Author)
  • Werner Paulus - , University of Münster (Author)
  • Christian Hartmann - , Hannover Medical School (MHH) (Author)
  • Ori Staszewski - , University of Freiburg (Author)
  • Marco Prinz - , University of Freiburg (Author)
  • Jürgen Hench - , University of Basel (Author)
  • Stephan Frank - , University of Basel (Author)
  • Yvonne M.H. Versleijen-Jonkers - , Radboud University Nijmegen (Author)
  • Marije E. Weidema - , Radboud University Nijmegen (Author)
  • Thomas Mentzel - , Medical care center Dermapathology Friedrichshafen/Lake Constance PartG (Author)
  • Klaus Griewank - , University of Duisburg-Essen (Author)
  • Enrique de Álava - , Spanish National Research Council (CSIC), University of Seville (Author)
  • Juan Díaz Martín - , Spanish National Research Council (CSIC) (Author)
  • Miguel A.Idoate Gastearena - , University Hospital Navarra (CUN) (Author)
  • Kenneth Tou En Chang - , KK Women's and Children's Hospital (Author)
  • Sharon Yin Yee Low - , Singapore Health Services (Author)
  • Adrian Cuevas-Bourdier - , Laboratoire National de Santé (Author)
  • Michel Mittelbronn - , Laboratoire National de Santé, Luxembourg Institute of Health, University of Luxembourg (Author)
  • Martin Mynarek - , University of Hamburg (Author)
  • Stefan Rutkowski - , University of Hamburg (Author)
  • Ulrich Schüller - , University of Hamburg, Research Institute Children's Cancer Center Hamburg (Author)
  • Viktor F. Mautner - , University of Hamburg (Author)
  • Jens Schittenhelm - , University Hospital Tübingen (Author)
  • Jonathan Serrano - , New York University (Author)
  • Matija Snuderl - , New York University (Author)
  • Reinhard Büttner - , University of Cologne (Author)
  • Thomas Klingebiel - , University Hospital Frankfurt (Author)
  • Rolf Buslei - , Hospital Sozialstiftung Bamberg (Author)
  • Manfred Gessler - , University of Würzburg (Author)
  • Pieter Wesseling - , Princess Máxima Center for Pediatric Oncology, Vrije Universiteit Amsterdam (VU) (Author)
  • Winand N.M. Dinjens - , Erasmus University Rotterdam (Author)
  • Sebastian Brandner - , University College London (Author)
  • Zane Jaunmuktane - , University College London (Author)
  • Iben Lyskjær - , University College London (Author)
  • Peter Schirmacher - , Heidelberg University  (Author)
  • Albrecht Stenzinger - , Heidelberg University  (Author)
  • Benedikt Brors - , German Cancer Research Center (DKFZ) (Author)
  • Hanno Glimm - , National Center for Tumor Diseases Dresden, Translational Functional Cancer Genomics Group, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK) Partner Site Dresden, National Center for Tumor Diseases (NCT) Dresden (Author)
  • Christoph Heining - , National Center for Tumor Diseases Dresden, German Cancer Consortium (Partner: DKTK, DKFZ), German Cancer Consortium (DKTK) Partner Site Dresden, National Center for Tumor Diseases (NCT) Dresden (Author)
  • Oscar M. Tirado - , Bellvitge Biomedical Research Institute (IDIBELL) (Author)
  • Miguel Sáinz-Jaspeado - , Bellvitge Biomedical Research Institute (IDIBELL) (Author)
  • Jaume Mora - , Hospital Sant Joan de Déu Barcelona (Author)
  • Javier Alonso - , Instituto de Salud Carlos III (Author)
  • Xavier Garcia del Muro - , University of Barcelona (Author)
  • Sebastian Moran - , Bellvitge Biomedical Research Institute (IDIBELL) (Author)
  • Manel Esteller - , Josep Carreras Leukaemia Research Institute , CIBER - Center for Biomedical Research Network, ICREA, University of Barcelona (Author)
  • Jamal K. Benhamida - , Memorial Sloan-Kettering Cancer Center (Author)
  • Marc Ladanyi - , Memorial Sloan-Kettering Cancer Center (Author)
  • Eva Wardelmann - , University of Münster (Author)
  • Cristina Antonescu - , Memorial Sloan-Kettering Cancer Center (Author)
  • Adrienne Flanagan - , Royal National Orthopaedic Hospital NHS Trust, University College London (Author)
  • Uta Dirksen - , University of Duisburg-Essen (Author)
  • Peter Hohenberger - , Heidelberg University  (Author)
  • Daniel Baumhoer - , University of Basel (Author)
  • Wolfgang Hartmann - , University of Münster (Author)
  • Christian Vokuhl - , University Hospital Schleswig-Holstein Campus Kiel (Author)
  • Uta Flucke - , Radboud University Nijmegen (Author)
  • Iver Petersen - , SRH Wald-Klinikum Gera , Friedrich Schiller University Jena (Author)
  • Gunhild Mechtersheimer - , Heidelberg University  (Author)
  • David Capper - , Charité – Universitätsmedizin Berlin (Author)
  • David T.W. Jones - , Hopp Children's Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ) (Author)
  • Stefan Fröhling - , German Cancer Research Center (DKFZ) (Author)
  • Stefan M. Pfister - , Hopp Children's Cancer Center Heidelberg (KiTZ), German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Andreas von Deimling - , Heidelberg University , German Cancer Research Center (DKFZ) (Author)

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.

Details

Original languageEnglish
Article number498
JournalNature communications
Volume12
Issue number1
Publication statusPublished - 1 Dec 2021
Peer-reviewedYes

External IDs

PubMed 33479225