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Stichel, Damian; Sill, Martin; Sahm, Felix; Reuss, David E; Blattner, Mirjam; Worst, Barbara; Heilig, Christoph E; Horak, Peter; Kreutzfeldt, Simon; Paff, Elke; Stark, Sebastian; Johann, Pascal; Selt, Florian; Ecker, Jonas; Sturm, Dominik; Pajtler, Kristian W; Wefers, Annika K; Ebrahimi, Azadeh; Suwala, Abigail; Fernández-Klett, Francisco; Casalini, Belén; Korshunov, Andrey; Hovestadt, Volker; Kommoss, Felix K F; Kriegsmann, Mark; Schick, Matthias; Milde, Till; Witt, Olaf; Kulozik, Andreas E; Kool, Marcel; Romero-Pérez, Laura; Grünewald, Thomas G P; Kirchner, Thomas; Platten, Michael; Unterberg, Andreas; Uhl, Matthias; Abdollahi, Amir; Debus, Jürgen; Hasselblatt, Martin; Paulus, Werner; Hartmann, Christian; Staszewski, Ori; Prinz, Marco; Hench, Jürgen; Frank, Stephan; Versleijen-Jonkers, Yvonne M H; Weidema, Marije E; Mentzel, Thomas; Griewank, Klaus; de Álava, Enrique; Martín, Juan Díaz; Gastearena, Miguel A Idoate; Chang, Kenneth Tou-En; Low, Sharon Yin Yee; Cuevas-Bourdier, Adrian; Mittelbronn, Michel; Mynarek, Martin; Rutkowski, Stefan; Schüller, Ulrich; Mautner, Viktor F; Schittenhelm, Jens; Serrano, Jonathan; Snuderl, Matija; Büttner, Reinhard; Klingebiel, Thomas; Buslei, Rolf; Gessler, Manfred; Wesseling, Pieter; Dinjens, Winand N M; Brandner, Sebastian; Jaunmuktane, Zane; Lyskjær, Iben; Schirmacher, Peter; Stenzinger, Albrecht; Brors, Benedikt; Glimm, Hanno; Heining, Christoph; Tirado, Oscar M; Sáinz-Jaspeado, Miguel; Mora, Jaume; Alonso, Javier; Del Muro, Xavier Garcia; Moran, Sebastian; Esteller, Manel; Ladanyi, Marc; Wardelmann, Eva; Antonescu, Cristina; Flanagan, Adrienne; Dirksen, Uta; Hohenberger, Peter; Baumhoer, Daniel; Hartmann, Wolfgang; Flucke, Uta; Petersen, Iver; Mechtersheimer, Gunhild; Capper, David; Jones, David T W; Fröhling, Stefan; Pfister, Stefan M; von Deimling, Andreas
Nature communications, 01/2021, Volume: 12, Issue: 1Journal Article
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.
