Expression of the FUS domain restores liposarcoma development in CHOP transgenic mice

Oncogene. 2002 Mar 7;21(11):1679-84. doi: 10.1038/sj.onc.1205220.


Fusion proteins created by chromosomal abnormalities are key components of mesenchymal cancer development. The most common chromosomal translocation in liposarcomas, t(12;16)(q13;p11), creates the FUS-CHOP fusion gene. In the past, we generated FUS-CHOP and CHOP transgenic mice and have shown that while FUS-CHOP transgenic develop liposarcomas, mice expressing CHOP, which lacks the FUS domain, display essentially normal white adipose tissue (WAT) development, suggesting that the FUS domain of FUS-CHOP plays a specific and critical role in the pathogenesis of liposarcoma. To test the significance of FUS and CHOP domain interactions within a living mouse, we generated mice expressing the FUS domain and crossed them with CHOP-transgenic mice to generate double-transgenic FUSxCHOP animals. Here we report that expression of the FUS domain restores liposarcoma development in CHOP-transgenic mice. Our results provide genetic evidence that FUS and CHOP domains function in trans for the mutual restoration of liposarcoma. These results identify a new mechanism of tumor-associated fusion genes and might have impact beyond myxoid liposarcoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipocytes / physiology
  • Animals
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • CCAAT-Enhancer-Binding Proteins / physiology*
  • Cell Differentiation
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Humans
  • Liposarcoma / etiology*
  • Liposarcoma / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Oncogene Proteins, Fusion / genetics*
  • RNA-Binding Protein FUS
  • Ribonucleoproteins / physiology*
  • Transcription Factor CHOP
  • Transcription Factors / physiology*


  • CCAAT-Enhancer-Binding Proteins
  • DDIT3 protein, human
  • Ddit3 protein, mouse
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Oncogene Proteins, Fusion
  • RNA-Binding Protein FUS
  • Ribonucleoproteins
  • TLS-CHOP fusion protein, human
  • Transcription Factors
  • Transcription Factor CHOP