Detection of myxoid liposarcoma-associated FUS-DDIT3 rearrangement variants including a newly identified breakpoint using an optimized RT-PCR assay

Mod Pathol. 2010 Oct;23(10):1307-15. doi: 10.1038/modpathol.2010.118. Epub 2010 Jun 25.

Abstract

Myxoid/round cell liposarcoma is characterized by the recurrent translocations t(12;16)(q13;p11) and, less commonly, t(12;22)(q13;q12), which fuse FUS or EWSR1, respectively, to DDIT3 on chromosome 12. Although a number of different variant breakpoints have been described, greater than 90% of all cases have one of the three different FUS-DDIT3 fusions, which may have clinical significance. To identify the individual breakpoints, a sequence-specific assay such as reverse transcription-PCR (RT-PCR) is needed. In this study, we optimized primer design to develop an RT-PCR assay for the detection of the most common translocations in formalin-fixed paraffin-embedded tissue specimens. We compared our assay with primers previously published for testing formalin-fixed paraffin-embedded specimens and achieved the most consistent results with our primers. We obtained RNA from 32 MLS cases, of which 27 carried one of the three common FUS-DDIT3 chimeric transcript types. Four of the negative cases were from very small biopsies with very low RNA concentration. One case was consistently negative by RT-PCR, but showed a FUS rearrangement by fluorescent in situ hybridization, suggesting that it may harbor one of the rarer FUS-DDIT3 chimeric types. In addition to the common fusions, our assay also identified a novel FUS-DDIT3 fusion between exon 9 of FUS and exon 3 of DDIT3 in one of the cases.

MeSH terms

  • Chromosome Breakpoints*
  • DNA Primers*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Liposarcoma, Myxoid / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction / methods*
  • Translocation, Genetic

Substances

  • DNA Primers
  • FUS-DDIT3 fusion protein, human
  • Oncogene Proteins, Fusion