Transcriptomic definition of molecular subgroups of small round cell sarcomas

J Pathol. 2018 May;245(1):29-40. doi: 10.1002/path.5053. Epub 2018 Mar 30.


Sarcoma represents a highly heterogeneous group of tumours. We report here the first unbiased and systematic search for gene fusions combined with unsupervised expression analysis of a series of 184 small round cell sarcomas. Fusion genes were detected in 59% of samples, with half of them being observed recurrently. We identified biologically homogeneous groups of tumours such as the CIC-fused (to DUX4, FOXO4 or NUTM1) and BCOR-rearranged (BCOR-CCNB3, BCOR-MAML3, ZC3H7B-BCOR, and BCOR internal duplication) tumour groups. VGLL2-fused tumours represented a more biologically and pathologically heterogeneous group. This study also refined the characteristics of some entities such as EWSR1-PATZ1 spindle cell sarcoma or FUS-NFATC2 bone tumours that are different from EWSR1-NFATC2 tumours and transcriptionally resemble CIC-fused tumour entities. We also describe a completely novel group of epithelioid and spindle-cell rhabdomyosarcomas characterized by EWSR1- or FUS-TFCP2 fusions. Finally, expression data identified some potentially new therapeutic targets or pathways. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: BCOR-rearranged; CIC-fused; EWSR1-PATZ1; FET-TFCP2; FUS-NFATC2; RNAseq; VGLL2-NCOA2; fusion genes; sarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Bone Neoplasms / genetics*
  • DNA-Binding Proteins / genetics
  • Gene Fusion / genetics
  • Humans
  • Muscle Proteins / genetics
  • Oncogene Proteins, Fusion / genetics*
  • Repressor Proteins / genetics
  • Sarcoma, Small Cell / genetics*
  • Transcription Factors / genetics
  • Transcriptome / genetics*


  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Muscle Proteins
  • Oncogene Proteins, Fusion
  • Repressor Proteins
  • TFCP2 protein, human
  • Transcription Factors
  • VGLL2 protein, human