Generation and characterization of a novel mouse model of synovial sarcoma
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Martin, Lauren Adria
issued: 2024-09-30T07:00:00Z
issued: 2019
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Synovial sarcoma is an aggressive soft-tissue sarcoma that most frequently affects adolescents and young adults and can arise in virtually any area of the body. The biologic behaviour of synovial sarcoma can vary depending on several factors and the 10-year survival rate has been estimated at only 50%. Synovial sarcoma is characterized by a pathognomonic t(X;18)(p11.2;q11.2) translocation which produces a fusion oncogene named SS18-SSX. The cell of origin of synovial sarcoma is currently unknown, although recent research indicates that it may arise from a mesenchymal stem/progenitor cell population. We have generated a unique mouse model of synovial sarcoma where the human SS18-SSX fusion oncogene is conditionally expressed in a population of mesenchymal progenitor cells using a Hic1Cʳᵉᴱᴿᵀ² driver developed by our lab. This model shows robust formation of synovial sarcoma with 100% penetrance and a mean latency period of 16 weeks. The mouse tumours were characterized histologically, using immunofluorescence and hematoxylin and eosin staining, and at the transcriptomic level using single-cell RNA-sequencing. Histologic analysis reveals characteristic cellular morphology and marker expression, while scRNA-seq analyses show that gene expression in these tumours parallels transcript profiles observed in human synovial sarcoma samples. Using this model, we can identify and isolate early neoplastic lesions prior to the development of grossly visible tumours; scRNA-seq of early lesions shows a partially-transformed phenotype and highlights cellular programs involved early in sarcomagenesis. We then generated two modified versions of this model through the addition of stabilized β-catenin (Ctnnb1ᴱˣ³Fᴵ) and knockout of SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (Smarcb1Fᴵ) to assess the effects of activated WNT/ β-catenin signaling and loss of Smarcb1, respectively. Both models show a decreased latency period and more aggres…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/71350
note: GENERATION AND CHARACTERIZATION OF A NOVEL MOUSE MODEL OF SYNOVIAL SARCOMA by Lauren Adria Martin DVM, University of Saskatchewan, 2013 BSc, University of Calgary, conferred 2010 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Cell and Developmental Biology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) August 2019 © Lauren Adria Martin, 2019 ii Committee Page The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, a thesis/dissertation entitled: Generation and characterization of a novel mouse model of synovial sarcoma submitted by Lauren Adria Martin in partial fulfillment of the requirements for the degree of Master of Science in Cell and Developmental Biology Examining Committee: Dr. T. Michael Underhill Supervisor Dr. Martin Hirst Supervisory Committee Member Dr. Torsten Nielsen Supervisory Committee Member Dr. Kelly McNagny Additional Examiner Additional Supervisory Committee Members: Dr. Stephen Yip Supervisory Committee Member iii Abstract Synovial sarcoma is an aggressive soft-tissue sarcoma that most frequently affects adolescents and young adults and can arise in virtually any area of the body. The biologic behaviour of synovial sarcoma can vary depending on several factors and the 10-year survival rate has been estimated at only 50%. Synovial sarcoma is characterized by a pathognomonic t(X;18)(p11.2;q11.2) translocation which produces a fusion oncogene named SS18-SSX. The cell of origin of synovial sarcoma is currently unknown, although recent research indicates that it may arise from a mesenchymal stem/progenitor cell population. We have generated a unique mouse model of synovial sarcoma where the human SS18-SSX fusion oncogene is conditionally expressed in a population of mesenchymal progenitor cells using a Hic1CreERT2 driver developed by our lab. This model shows robus…
has type: Thesis/Dissertation
date issued: 2019-09
is shown at: 10.14288/1.0380491
language: eng
degree discipline: Cell and Developmental Biology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/71350