Koelsche, Christian ORCID: 0000-0001-8763-8864, Schrimpf, Daniel, Stichel, Damian, Sill, Martin, Sahm, Felix ORCID: 0000-0001-5441-1962, Reuss, David E., Blattner, Mirjam, Worst, Barbara, Heilig, Christoph E. ORCID: 0000-0001-8869-1421, Beck, Katja, Horak, Peter ORCID: 0000-0003-4536-9306, Kreutzfeldt, Simon, Paff, Elke, Stark, Sebastian, Johann, Pascal, Selt, Florian, Ecker, Jonas, Sturm, Dominik, Pajtler, Kristian W., Reinhardt, Annekathrin, Wefers, Annika K. ORCID: 0000-0001-9394-8519, Sievers, Philipp, Ebrahimi, Azadeh ORCID: 0000-0001-7354-1746, Suwala, Abigail, Fernandez-Klett, Francisco, Casalini, Belen, Korshunov, Andrey, Hovestadt, Volker, Kommoss, Felix K. F., Kriegsmann, Mark ORCID: 0000-0002-7319-3646, Schick, Matthias, Bewerunge-Hudler, Melanie, Milde, Till ORCID: 0000-0002-7267-1052, Witt, Olaf, Kulozik, Andreas E., Kool, Marcel, Romero-Perez, Laura, Gruenewald, Thomas G. P., Kirchner, Thomas, Wick, Wolfgang, Platten, Michael ORCID: 0000-0002-4746-887X, Unterberg, Andreas, Uhl, Matthias, Abdollahi, Amir, Debus, Juergen, Lehner, Burkhard, Thomas, Christian, Hasselblatt, Martin, Paulus, Werner, Hartmann, Christian, Staszewski, Ori, Prinz, Marco, Hench, Juergen, Frank, Stephan, Versleijen-Jonkers, Yvonne M. H., Weidema, Marije E., Mentzel, Thomas, Griewank, Klaus, de Alava, Enrique ORCID: 0000-0001-8400-046X, Martin, Juan Diaz, Gastearena, Miguel A. Idoate, Chang, Kenneth Tou-En, Low, Sharon Yin Yee, Cuevas-Bourdier, Adrian, Mittelbronn, Michel ORCID: 0000-0002-2998-052X, Mynarek, Martin, Rutkowski, Stefan, Schueller, Ulrich, Mautner, Viktor F., Schittenhelm, Jens, Serrano, Jonathan, Snuderl, Matija ORCID: 0000-0003-0752-0917, Buettner, Reinhard, Klingebiel, Thomas, Buslei, Rolf, Gessler, Manfred ORCID: 0000-0002-7915-6045, Wesseling, Pieter, Dinjens, Winand N. M., Brandner, Sebastian ORCID: 0000-0002-9821-0342, Jaunmuktane, Zane, Lyskjaer, Iben ORCID: 0000-0003-3446-1182, Schirmacher, Peter, Stenzinger, Albrecht, Brors, Benedikt ORCID: 0000-0001-5940-3101, Glimm, Hanno, Heining, Christoph, Tirado, Oscar M., Sainz-Jaspeado, Miguel, Mora, Jaume, Alonso, Javier ORCID: 0000-0002-6287-8391, del Muro, Xavier Garcia, Moran, Sebastian, Esteller, Manel, Benhamida, Jamal K., Ladanyi, Marc, Wardelmann, Eva, Antonescu, Cristina, Flanagan, Adrienne, Dirksen, Uta, Hohenberger, Peter, Baumhoer, Daniel, Hartmann, Wolfgang, Vokuhl, Christian, Flucke, Uta, Petersen, Iver, Mechtersheimer, Gunhild, Capper, David ORCID: 0000-0003-1945-497X, Jones, David T. W., Froehling, Stefan, Pfister, Stefan M. and von Deimling, Andreas ORCID: 0000-0002-5863-540X (2021). Sarcoma classification by DNA methylation profiling. Nat. Commun., 12 (1). BERLIN: NATURE RESEARCH. ISSN 2041-1723

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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. Sarcomas are morphologically heterogeneous tumours rendering their classification challenging. Here the authors developed a classifier using DNA methylation data from several soft tissue and bone sarcoma subtypes, which has the potential to improve classification for research and clinical purposes.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Koelsche, ChristianUNSPECIFIEDorcid.org/0000-0001-8763-8864UNSPECIFIED
Schrimpf, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stichel, DamianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sill, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sahm, FelixUNSPECIFIEDorcid.org/0000-0001-5441-1962UNSPECIFIED
Reuss, David E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blattner, MirjamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Worst, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heilig, Christoph E.UNSPECIFIEDorcid.org/0000-0001-8869-1421UNSPECIFIED
Beck, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Horak, PeterUNSPECIFIEDorcid.org/0000-0003-4536-9306UNSPECIFIED
Kreutzfeldt, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paff, ElkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stark, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johann, PascalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Selt, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ecker, JonasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sturm, DominikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pajtler, Kristian W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinhardt, AnnekathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wefers, Annika K.UNSPECIFIEDorcid.org/0000-0001-9394-8519UNSPECIFIED
Sievers, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ebrahimi, AzadehUNSPECIFIEDorcid.org/0000-0001-7354-1746UNSPECIFIED
Suwala, AbigailUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernandez-Klett, FranciscoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Casalini, BelenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korshunov, AndreyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hovestadt, VolkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kommoss, Felix K. F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kriegsmann, MarkUNSPECIFIEDorcid.org/0000-0002-7319-3646UNSPECIFIED
Schick, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bewerunge-Hudler, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milde, TillUNSPECIFIEDorcid.org/0000-0002-7267-1052UNSPECIFIED
Witt, OlafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kulozik, Andreas E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kool, MarcelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Romero-Perez, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruenewald, Thomas G. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kirchner, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wick, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Platten, MichaelUNSPECIFIEDorcid.org/0000-0002-4746-887XUNSPECIFIED
Unterberg, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Uhl, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abdollahi, AmirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Debus, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehner, BurkhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hasselblatt, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paulus, WernerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Staszewski, OriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prinz, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hench, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frank, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Versleijen-Jonkers, Yvonne M. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weidema, Marije E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mentzel, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Griewank, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Alava, EnriqueUNSPECIFIEDorcid.org/0000-0001-8400-046XUNSPECIFIED
Martin, Juan DiazUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gastearena, Miguel A. IdoateUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chang, Kenneth Tou-EnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Low, Sharon Yin YeeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cuevas-Bourdier, AdrianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mittelbronn, MichelUNSPECIFIEDorcid.org/0000-0002-2998-052XUNSPECIFIED
Mynarek, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rutkowski, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schueller, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mautner, Viktor F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schittenhelm, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Serrano, JonathanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Snuderl, MatijaUNSPECIFIEDorcid.org/0000-0003-0752-0917UNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klingebiel, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buslei, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gessler, ManfredUNSPECIFIEDorcid.org/0000-0002-7915-6045UNSPECIFIED
Wesseling, PieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dinjens, Winand N. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brandner, SebastianUNSPECIFIEDorcid.org/0000-0002-9821-0342UNSPECIFIED
Jaunmuktane, ZaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lyskjaer, IbenUNSPECIFIEDorcid.org/0000-0003-3446-1182UNSPECIFIED
Schirmacher, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stenzinger, AlbrechtUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brors, BenediktUNSPECIFIEDorcid.org/0000-0001-5940-3101UNSPECIFIED
Glimm, HannoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heining, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tirado, Oscar M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sainz-Jaspeado, MiguelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mora, JaumeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alonso, JavierUNSPECIFIEDorcid.org/0000-0002-6287-8391UNSPECIFIED
del Muro, Xavier GarciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moran, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Esteller, ManelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benhamida, Jamal K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ladanyi, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wardelmann, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antonescu, CristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Flanagan, AdrienneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dirksen, UtaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hohenberger, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baumhoer, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vokuhl, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Flucke, UtaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petersen, IverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mechtersheimer, GunhildUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Capper, DavidUNSPECIFIEDorcid.org/0000-0003-1945-497XUNSPECIFIED
Jones, David T. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Froehling, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfister, Stefan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Deimling, AndreasUNSPECIFIEDorcid.org/0000-0002-5863-540XUNSPECIFIED
URN: urn:nbn:de:hbz:38-608224
DOI: 10.1038/s41467-020-20603-4
Journal or Publication Title: Nat. Commun.
Volume: 12
Number: 1
Date: 2021
Publisher: NATURE RESEARCH
Place of Publication: BERLIN
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MOLECULAR CLASSIFICATION; MEDULLOBLASTOMA; MULTICENTER; SUBGROUPS; DIAGNOSIS; MEDICINE; DEFINES; CANCERS; SYSTEMMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60822

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