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Liposarcoma initiated by FUS/TLS-CHOP: the FUS/TLS domain plays a critical role in the pathogenesis of liposarcoma

Oncogene volume 19, pages 6015–6022 (2000)Cite this article

Abstract

The most common chromosomal translocation in liposarcomas, t(12;16)(q13;p11), creates the FUS/TLS-CHOP fusion gene. We previously developed a mouse model of liposarcoma by expressing FUS-CHOP in murine mesenchymal stem cells. In order to understand how FUS-CHOP can initiate liposarcoma, we have now generated transgenic mice expressing altered forms of the FUS-CHOP protein. Transgenic mice expressing high levels of CHOP, which lacks the FUS domain, do not develop any tumor despite its tumorigenicity in vitro and widespread activity of the EF1α promoter. These animals consistently show the accumulation of a glycoprotein material within the terminally differentiated adipocytes, a characteristic figure of liposarcomas associated with FUS-CHOP. On the contrary, transgenic mice expressing the altered form of FUS-CHOP created by the in frame fusion of the FUS domain to the carboxy end of CHOP (CHOP-FUS) developed liposarcomas. No tumors of other tissues were found in these transgenic mice despite widespread activity of the EF1α promoter. The characteristics of the liposarcomas arising in the CHOP-FUS mice were very similar to those previously observed in our FUS-CHOP transgenic mice indicating that the FUS domain is required not only for transformation but also influences the phenotype of the tumor cells. These results provide evidence that the FUS domain of FUS-CHOP plays a specific and critical role in the pathogenesis of liposarcoma.

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Acknowledgements

We are grateful to Dr R Arévalo for providing the histological facilities. We are indebted to Dr C Cobaleda for help in the preparation of the manuscript, and specific thanks to JC Villoria-Terrón and JF Martín-Martín for excellent technical advice. This work has been supported by European Commission (BMH4-CT96-0375), DGCYT (PB96-0816, 1FD97-0360 and 1FD97-1126), Fundación Científica of the AECC, FIS (99/0935), and NIH grant (1 R01 CA79955-01).

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Authors and Affiliations

  1. Instituto de Bilogia Molecular y Celular del Cancer, Centro de Investigacion del Cancer, CSIC/Universidad de Salamanca, Campus Unamuno, 37007, Salamanca, Spain

    J Pérez-Losada, M Sánchez-Martín, M A Rodríguez-García, P A Pérez-Mancera & I Sánchez-García

  2. Area de Reproducción Animal, Centro de Investigación y Tecnología, Ctra de la Coruña km 5.9, 28040, Madrid, Spain

    B Pintado

  3. Servicio de Anatomía Patológica, Universidad de Salamanca, Campus Unamuno, 37007, Salamanca, Spain

    T Flores

  4. Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Campus Unamuno, 37007, Salamanca, Spain

    E Battaner

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  1. J Pérez-Losada
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Pérez-Losada, J., Sánchez-Martín, M., Rodríguez-García, M. et al. Liposarcoma initiated by FUS/TLS-CHOP: the FUS/TLS domain plays a critical role in the pathogenesis of liposarcoma. Oncogene 19, 6015–6022 (2000). https://doi.org/10.1038/sj.onc.1204018

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