CIC-DUX sarcomas demonstrate frequent MYC amplification and ETS-family transcription factor expression

Mod Pathol. 2015 Jan;28(1):57-68. doi: 10.1038/modpathol.2014.83. Epub 2014 Jun 20.


Recent molecular advances have identified a novel, clinically aggressive subgroup of undifferentiated round cell sarcomas defined molecularly by oncogenic fusion of the gene, CIC, and either DUX4 or its paralog, DUX4L, herein termed CIC-DUX sarcomas. Morphologically, CIC-DUX sarcomas are round cell sarcomas with high-grade nuclear features, including vesicular chromatin and nucleoli, patchy clear cell foci, myxoid change, and necrosis. Here, we studied a cohort of 10 cases, including 6 newly identified cases, 2 with paired metastases. Given our prior observation of trisomy 8 in these tumors, we assayed for amplification and expression of MYC (c-Myc) and representative downstream targets. Trisomy 8 was detected in 5/7 testable cases, with further amplification of MYC locus in 6/7 testable cases and immunohistochemical expression of MYC in 10/10. The canonical MYC transcriptional target, p21, but not MTDH, was differentially expressed compared with Ewing sarcomas. Given prior observation of induction of ETS-family transcription factors by the fusion oncoprotein, we assayed and identified highly prevalent positivity for ERG (9/10) and FLI1 (8/8). These findings are cautionary regarding use of these immunostains in prospective case workup, whereas the prevalent MYC amplification may represent a therapeutically targetable oncogenic pathway in CIC-DUX sarcomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Gene Amplification
  • Genes, myc / genetics*
  • Homeodomain Proteins / genetics
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Oncogene Proteins, Fusion
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-ets / biosynthesis*
  • Repressor Proteins / genetics
  • Retrospective Studies
  • Sarcoma, Small Cell / genetics*
  • Sarcoma, Small Cell / pathology
  • Soft Tissue Neoplasms / genetics*
  • Soft Tissue Neoplasms / pathology
  • Young Adult


  • CIC protein, human
  • DUX4L1 protein, human
  • Homeodomain Proteins
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins