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(American Journal of Pathology. 2006;168:1642-1653.)
© 2006 American Society for Investigative Pathology

The Myxoid/Round Cell Liposarcoma Fusion Oncogene FUS-DDIT3 and the Normal DDIT3 Induce a Liposarcoma Phenotype in Transfected Human Fibrosarcoma Cells

Katarina Engström*, Helena Willén{dagger}, Christina Kåbjörn-Gustafsson{ddagger}, Carola Andersson{ddagger}, Marita Olsson§, Melker Göransson{ddagger}, Sofia Järnum{ddagger}, Anita Olofsson{ddagger}, Elisabeth Warnhammar* and Pierre Åman{ddagger}

From the Department of Oncology,* and the Lundberg Laboratory for Cancer Research, Department of Pathology,{ddagger} the Gothenburg, University, Sahlgrenska University Hospital, Gothenburg; the Department of Genetics and Pathology,{dagger} Rudbecklaboratoriet, Uppsala; and the Swegene Facility for Bioinformatics,§ Gothenburg, University/Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden

Myxoid/round cell liposarcoma (MLS/RCLS) is the most common subtype of liposarcoma. Most MLS/RCLS carry a t(12;16) translocation, resulting in a FUS-DDIT3 fusion gene. We investigated the role of the FUS-DDIT3 fusion in the development of MLS/RCLS in FUS-DDIT3- and DDIT3-transfected human HT1080 sarcoma cells. Cells expressing FUS-DDIT3 and DDIT3 grew as liposarcomas in severe combined immunodeficient mice and exhibited a capillary network morphology that was similar to networks of MLS/RCLS. Microarray-based comparison of HT1080, the transfected cells, and an MLS/RCLS-derived cell line showed that the FUS-DDIT3- and DDIT3-transfected variants shifted toward an MLS/RCLS-like expression pattern. DDIT3-transfected cells responded in vitro to adipogenic factors by accumulation of fat and transformation to a lipoblast-like morphology. In conclusion, because the fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype when expressed in a primitive sarcoma cell line, MLS/RCLS may develop from cell types other than preadipocytes. This may explain the preferential occurrence of MLS/RCLS in nonadipose tissues. In addition, development of lipoblasts and the typical MLS/RCLS capillary network could be an effect of the DDIT3 transcription factor partner of the fusion oncogene.





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