1. Sarcoma classification by DNA methylation profiling.
- Author
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Koelsche C, Schrimpf D, Stichel D, Sill M, Sahm F, Reuss DE, Blattner M, Worst B, Heilig CE, Beck K, Horak P, Kreutzfeldt S, Paff E, Stark S, Johann P, Selt F, Ecker J, Sturm D, Pajtler KW, Reinhardt A, Wefers AK, Sievers P, Ebrahimi A, Suwala A, Fernández-Klett F, Casalini B, Korshunov A, Hovestadt V, Kommoss FKF, Kriegsmann M, Schick M, Bewerunge-Hudler M, Milde T, Witt O, Kulozik AE, Kool M, Romero-Pérez L, Grünewald TGP, Kirchner T, Wick W, Platten M, Unterberg A, Uhl M, Abdollahi A, Debus J, Lehner B, Thomas C, Hasselblatt M, Paulus W, Hartmann C, Staszewski O, Prinz M, Hench J, Frank S, Versleijen-Jonkers YMH, Weidema ME, Mentzel T, Griewank K, de Álava E, Martín JD, Gastearena MAI, Chang KT, Low SYY, Cuevas-Bourdier A, Mittelbronn M, Mynarek M, Rutkowski S, Schüller U, Mautner VF, Schittenhelm J, Serrano J, Snuderl M, Büttner R, Klingebiel T, Buslei R, Gessler M, Wesseling P, Dinjens WNM, Brandner S, Jaunmuktane Z, Lyskjær I, Schirmacher P, Stenzinger A, Brors B, Glimm H, Heining C, Tirado OM, Sáinz-Jaspeado M, Mora J, Alonso J, Del Muro XG, Moran S, Esteller M, Benhamida JK, Ladanyi M, Wardelmann E, Antonescu C, Flanagan A, Dirksen U, Hohenberger P, Baumhoer D, Hartmann W, Vokuhl C, Flucke U, Petersen I, Mechtersheimer G, Capper D, Jones DTW, Fröhling S, Pfister SM, and von Deimling A
- Subjects
- Bone Neoplasms classification, Bone Neoplasms diagnosis, Cohort Studies, DNA Copy Number Variations genetics, Humans, Internet, Reproducibility of Results, Sarcoma classification, Sarcoma diagnosis, Sensitivity and Specificity, Soft Tissue Neoplasms classification, Soft Tissue Neoplasms diagnosis, Algorithms, Bone Neoplasms genetics, DNA Methylation, Machine Learning, Sarcoma genetics, Soft Tissue Neoplasms genetics
- 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.
- Published
- 2021
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