Creating a molecular toolbox to uncover the role of EWS-ATF1 in the development of Clear Cell Carcinoma

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State: Public
Version: After imprimatur
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Serval ID
serval:BIB_F0EE17E7C669
Type
A Master's thesis.
Publication sub-type
Master (thesis) (master)
Collection
Publications
Institution
Title
Creating a molecular toolbox to uncover the role of EWS-ATF1 in the development of Clear Cell Carcinoma
Author(s)
FISCHER J.
Director(s)
STAMENKOVIC I.
Codirector(s)
FUSCO C.
Institution details
Université de Lausanne, Faculté de biologie et médecine
Publication state
Accepted
Issued date
2019
Language
english
Number of pages
17
Abstract
Clear Cell Sarcoma (CCS) is a malignant tumor caused by a t(12;22) translocation in cells of mesenchymal linage, and leads to the expression of a particular oncogene, EWS-ATF1. While studies in mouse models have confirmed the role of EWS-ATF1 in causing malignant transformation, we know very little about the genetic and epigenetic events succeeding the expression of this chimeric protein. In particular, we do not know if the effect EWS-ATF1 has on chromatin resembles that of EWS-FLI1, the oncogene responsible for Ewing’s sarcoma, as both proteins contain the same EWS sequence.
The ATF1 portion of the CCS oncogenic protein is a transcriptional factor of the basic helix-loop-helix leucine-zipper family. When fused with EWS, we do not know if it maintains the same target genes as well as the same enzymatic role, nor do we know if the habitual signaling control that regulates its activity changes in a significant way.
We plan to perform a set of experiments, first with the purpose of testing the recruitment of EWS-ATF1 on the chromatin, then measuring the activity of the BAF remodeling complex (as shown with EWS-FLI1) and finally determining the transcriptional role of ATF1 in CCS.
The argument of this thesis is the description of the project that allowed the construction of a molecular toolbox composed of lentiviral vectors capable of transducing EWS-ATF1 mutants targeting the functional parts of both moieties of the chimera in CCS models.
Keywords
EWS-ATF1, clear cell sarcoma, lentiviral vectors, fusion oncogene, EWS-FLI1, BAF complex, basic leucin zipper
Create date
07/09/2020 11:13
Last modification date
09/10/2020 6:25
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