Sarcoma classification by DNA methylation profiling

Koelsche, Christian; Schrimpf, Daniel; Stichel, Damian; Sill, Martin; Sahm, Felix; Reuss, David E.; Blattner, Mirjam; Worst, Barbara; Heilig, Christoph E.; Beck, Katja; Horak, Peter; Kreutzfeldt, Simon; Paff, Elke; Stark, Sebastian; Johann, Pascal; Selt, Florian; Ecker, Jonas; Sturm, Dominik; Pajtler, Kristian W.; Reinhardt, Annekathrin; Wefers, Annika K.; Sievers, Philipp; Ebrahimi, Azadeh; Suwala, Abigail; Fernandez-Klett, Francisco; Casalini, Belen; Korshunov, Andrey; Hovestadt, Volker; Kommoss, Felix K. F.; Kriegsmann, Mark; Schick, Matthias; Bewerunge-Hudler, Melanie; Milde, Till; Witt, Olaf; Kulozik, Andreas E.; Kool, Marcel; Romero-Perez, Laura; Gruenewald, Thomas G. P.; Kirchner, Thomas; Wick, Wolfgang; Platten, Michael; Unterberg, Andreas; Uhl, Matthias; Abdollahi, Amir; Debus, Jürgen; Lehner, Burkhard; Thomas, Christian; 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 Alava, Enrique; Martin, Juan Diaz; Gastearena, Miguel A. Idoate; Chang, Kenneth Tou-En; Low, Sharon Yin Yee; Cuevas-Bourdier, Adrian; Mittelbronn, Michel; Mynarek, Martin; Rutkowski, Stefan; Schueller, Ulrich; Mautner, Viktor F.; Schittenhelm, Jens; Serrano, Jonathan; Snuderl, Matija; Buettner, Reinhard; Klingebiel, Thomas; Buslei, Rolf; Gessler, Manfred; Wesseling, Pieter; Dinjens, Winand N. M.; Brandner, Sebastian; Jaunmuktane, Zane; Lyskjaer, Iben; Schirmacher, Peter; Stenzinger, Albrecht; Brors, Benedikt; Glimm, Hanno; Heining, Christoph; Tirado, Oscar M.; Sainz-Jaspeado, Miguel; Mora, Jaume; Alonso, Javier; 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; Jones, David T. W.; Froehling, Stefan; Pfister, Stefan M. and Deimling, Andreas von (2021): Sarcoma classification by DNA methylation profiling. In: Nature Communications, Vol. 12, No. 1, 498

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
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• Language: English