Sarcoma classification by DNA methylation profiling

Nat Commun. 2021 Jan 21;12(1):498. doi: 10.1038/s41467-020-20603-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Bone Neoplasms / classification
  • Bone Neoplasms / diagnosis
  • Bone Neoplasms / genetics*
  • Cohort Studies
  • DNA Copy Number Variations / genetics
  • DNA Methylation*
  • Humans
  • Internet
  • Machine Learning*
  • Reproducibility of Results
  • Sarcoma / classification
  • Sarcoma / diagnosis
  • Sarcoma / genetics*
  • Sensitivity and Specificity
  • Soft Tissue Neoplasms / classification
  • Soft Tissue Neoplasms / diagnosis
  • Soft Tissue Neoplasms / genetics*