The effect of Imp-2 on Ewing sarcoma cancer stem cells: when epigenetics orchestrate tumor growth


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A Master's thesis.
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Master (thesis) (master)
The effect of Imp-2 on Ewing sarcoma cancer stem cells: when epigenetics orchestrate tumor growth
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Université de Lausanne, Faculté de biologie et médecine
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Ewing's sarcoma family tumors
Ewing sarcoma is part of the Ewing's sarcoma family tumors (ESFTs) that includes peripheral primitive neuroectodermal tumor (PNET), extraosseous ewing sarcoma, Askin's tumor and atypical Ewing sarcoma. These tumors share histological and immunohistochemical similarities and display a single chromosomal translocation. ESFT is the second most frequent malignant bone tumor, after osteosarcoma, of adolescents and young adults. ESFTs are very aggressive and often relapse after treatment.
Ewing sarcoma, on which this work will focus, occurs predominantly in the femur, the pelvis and less commonly in the upper extremities, axial skeleton, ribs and face with a peak incidence between 10 and 15 years of age. The histology of these tumors reflects poor differentiation and presents as small round cells with a halo of cytoplasm around the nucleus. They are therefore often referred to as small round blue cell tumors. Immunohistochemical analysis of ESFT reveals expression of the lymphoid cell adhesion receptor CD99, neural markers including NSE, S-100, synaptophysin and CD56 and mesenchymal markers including vimentin. Macroscopically, Ewing sarcoma is grey- white with zones of necrosis and fibrosis. It is associated with a survival rate of 65% at 5 years if treated with current multimodal therapy, which includes surgery, chemotherapy and radiation. However, Ewing sarcoma often displays multidrug resistance, which explains the frequent relapse.
The underlying event in Ewing sarcoma pathogenesis is the non-random balanced chromosomal translocation between chromosome 11 and chromosome 22, t(11q23;22q12). It causes fusion between EWS gene on chromosome 22q12 and an ETS family gene on chromosome 11q24 (FLI gene in 85% of cases or ERG, ETV1, ETV2, FEV) (1). This translocation plays an essential role in the development and the maintenance of ESFT (2) and it is also used for diagnosis by FISH and RT-PCR.
The fusion gene formed encodes an aberrant transcription factor, which drives the expression or repression of genes implicated in regulation of cell proliferation and transformation by binding to their promoters and thus playing a crucial role in Ewing sarcoma pathogenesis.
Ewing sarcoma, epigenetics, Imp-2, CSCs
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31/08/2016 15:32
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20/08/2019 16:32
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