Sarcoma classification by DNA methylation profiling.

  • Luxembourg Center of Neuropathology
January 21, 2021 By:
  • 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
  • Fernandez-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-Perez L
  • Grunewald 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 Alava E
  • Martin JD
  • Gastearena MAI
  • Chang KT
  • Low SYY
  • Cuevas-Bourdier A
  • Mittelbronn M
  • Mynarek M
  • Rutkowski S
  • Schuller U
  • Mautner VF
  • Schittenhelm J
  • Serrano J
  • Snuderl M
  • Buttner R
  • Klingebiel T
  • Buslei R
  • Gessler M
  • Wesseling P
  • Dinjens WNM
  • Brandner S
  • Jaunmuktane Z
  • Lyskjaer I
  • Schirmacher P
  • Stenzinger A
  • Brors B
  • Glimm H
  • Heining C
  • Tirado OM
  • Sainz-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
  • Frohling S
  • Pfister SM
  • von Deimling A.

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.

2021 Jan. Nat Commun.12(1):498.
Other information