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Translational molecular pathology of myxoid liposarcoma and leiomyosarcoma of soft tissue
The aim of this thesis is to gain more insight in the molecular pathology of soft tissue sarcomas, especially leiomyosarcoma and myxoid liposarcoma. The group of soft tissue sarcomas constitute a large number of different, mostly rare, neoplasms, each with their own histopathology, genetic profile and clinical features. Here we focus on the molecular profile of these two soft tissue tumours and performed studies to identify potential targets for specific therapeutic strategies. Leiomyosarcomas are characterized by a complex genetic profile which makes it difficult to identify targets for treatment. We here show that MED12 mutations are restricted to uterine smooth muscle tumours, and describe the occurrence of non-recurrent translocations in two cases of soft tissue leiomyosarcomas. Next, we show high expression of the Bcl family members in leiomyosarcomas, and using cell lines we could demonstrate that these proteins play a role in chemoresistance. Myxoid liposarcomas have a well-defined recurrent translocation. We show expression of the cancer-testis antigen NY-ESO-1 in a large proportion of tumours, providing options for immunotherapy. We present a novel, spontaneously immortalized myxoid liposarcoma cell line which was used for a largescale drug screen, resulting in the identification of a promising novel target.
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- All authors
- Graaff, M.A. de
- Supervisor
- Bovée, J.V.M.G.
- Co-supervisor
- Szuhai, K.
- Committee
- Gelderblom, A.J.; Debiec-Rychter, M.; Danen, E.
- Qualification
- Doctor (dr.)
- Awarding Institution
- Department of Pathology, Medicine, Leiden University
- Date
- 2017-02-07
- ISBN (print)
- 9789463321303
Funding
- Sponsorship
- Liddy Shriver Sarcoma Initiative