A cryptic EWSR1::DDIT3 fusion in myxoid liposarcoma: Potential pitfalls with FISH and cytogenetics

Genes Chromosomes Cancer. 2023 Mar;62(3):167-170. doi: 10.1002/gcc.23103. Epub 2022 Nov 24.


Myxoid liposarcoma (MLS) is molecularly characterized by fusions involving the DDIT3 gene in chromosome band 12q13; the fusion partner is FUS in band 16p11 in 90-95% of the cases and EWSR1 in band 22q12 in the remaining 5-10%. Hence, molecular studies, often fluorescence in situ hybridization (FISH) for DDIT3 rearrangement, are useful for establishing a correct diagnosis. Although all MLS tumors should have DDIT3 fusions, it is important to be aware of reasons for potential false-negative results. We here present a case of MLS that was negative for FISH for DDIT3, that showed an unexpected t(11;22) at G-banding, but that displayed a characteristic EWSR1::DDIT3 fusion at RNA-sequencing. The results suggest that neoplasia-associated fusions that, due to the transcriptional orientations of the two genes involved, cannot arise through only two double-strand breaks are more likely to be associated with negative FISH-findings and unexpected karyotypes.

Keywords: FISH; cryptic; fusion; liposarcoma; transcriptional orientation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Humans
  • In Situ Hybridization, Fluorescence
  • Liposarcoma* / genetics
  • Liposarcoma, Myxoid* / genetics
  • Liposarcoma, Myxoid* / pathology
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • RNA-Binding Protein EWS / genetics
  • Transcription Factor CHOP / genetics


  • Oncogene Proteins, Fusion
  • DDIT3 protein, human
  • Transcription Factor CHOP
  • EWSR1 protein, human
  • RNA-Binding Protein EWS