Chromosome rearrangements that lead to formation of fusion genes have been identified in many types of leukemia and solid tumors. Around 700 different fusion oncogenes are currently reported in human neoplasias. Many of them were found to transform cells in culture and to induce tumors in transgenic mice, showing their importance in tumor development. Many fusion genes are associated with only one type of tumors. The tumor type specificity suggests that their products interact with distinct differentiation controlling gene programs and cell types.
The aim of our research is to investigate the activities of the FET group of fusion oncogenes. They all encode chimeric transcription factor proteins containing a C-terminal DNA binding transcription factor part juxtaposed to an ectopic N-terminal protein interacting part. The FET oncogenes are strictly tumor type specific.
We have developed experimental systems to study the abnormal transcription factor activity and downstream effects of FET-oncogenes. We hope to increase our understanding of how their activities lead to tumor formation and how they interact with growth and differentiation controlling gene programs in different cell types. Many observations suggest that tumor development is initiated in stem or precursor cells and our current research focus on such cells. Our main experimental activities focus on the myxoid liposarcoma/round cell sarcoma specific FUS-CHOP and the Ewing sarcoma EWS-FLI1 fusion oncogenes and the interaction of their protein products with the control of cell growth, differentiation, stress, stemness and senescence.
Experimental systems: tumor cell lines, stemcell, and xenograft models. Methods: single cell expression analysis, advanced microscopy, and protein–protein interaction studies using recombinant proteins. Experimental findings are confirmed with studies on human tumor tissues.
Pierre Åman, PhD, Professor.
Katarina Engström, MD, PhD, Associated clinician, Oncology.
Christer Thomsen, PhD, student.
Christina Kåbjörn, MD, Pathologist, PhD student
Rikard Runnberg, PhD student.
Pernilla Grundevik, Technician.