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    Cassette Exon RNA Splicing Altered in Ewing Sarcoma Is Characterized by Higher Guanine-Cytosine Content and Lower Splice Site Strength Indicative of Intron-Definition Splicing

    Cover for Cassette Exon RNA Splicing Altered in Ewing Sarcoma Is Characterized by Higher Guanine-Cytosine Content and Lower Splice Site Strength Indicative of Intron-Definition Splicing
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    View/Open: Graham_georgetown_0076D_15109.pdf (24.MB) Bookview

    Creator
    Graham, Garrett Thomas
    Advisor
    Toretsky, Jeffrey A
    ORCID
    0000-0002-1097-0962
    Abstract
    Ewing sarcoma (EwS) is a pediatric cancer that typically presents at a mean of 15 years of age and is the second most common bone tumor in children and adolescents. While there have been substantial investigations into the mechanism of EwS oncogenesis, few of these findings have translated to improved therapeutics, and treatment of EwS has largely remained static for the last 30 years. Patients that present with localized EwS have an approximately 70% 5-year survival rate whereas patients that present with metastatic EwS have only a 30% 5-year survival rate. New approaches to understanding the oncogenic process and potential vulnerabilities behind EwS are badly needed, as targeted therapeutics for EwS patients have the opportunity to drastically improve long-term outcomes and reduce systemic effects. In this dissertation I present first the creation of a model to study EwS using bone marrow-derived human mesenchymal stem cells (hMSC-BM), as the lack of patient samples presents a substantial barrier to EwS research. I then describe my efforts to create a reference transcriptome using long-read sequencing that is more comprehensive than commonly used reference transcriptomes. I use this transcriptome to quantify mRNA splicing in tumor samples, followed by a detailed analysis of sequence features associated with altered RNA splicing in EwS.
    Description
    Ph.D.
    Permanent Link
    http://hdl.handle.net/10822/1064766
    Date Published
    2021
    Subject
    Ewing sarcoma; EWS-FLI1; GC content; RNA splicing; Oncology; Bioinformatics; Cytology; Oncology; Bioinformatics; Cellular biology;
    Type
    thesis
    Publisher
    Georgetown University
    Extent
    325 leaves
    Collections
    • Graduate Theses and Dissertations - Tumor Biology
    Metadata
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    • Cover for Cassette Exon RNA Splicing Altered in Ewing Sarcoma Is Characterized by Higher Guanine-Cytosine Content and Lower Splice Site Strength Indicative of Intron-Definition Splicing

      Cassette Exon RNA Splicing Altered in Ewing Sarcoma Is Characterized by Higher Guanine-Cytosine Content and Lower Splice Site Strength Indicative of Intron-Definition Splicing 

      Graham, Garrett Thomas (Georgetown University, 2021)
      Ewing sarcoma (EwS) is a pediatric cancer that typically presents at a mean of 15 years of age and is the second most common bone tumor in children and adolescents. While there have been substantial investigations into the ...
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    Georgetown University Seal
    ©2009 - 2023 Georgetown University Library
    37th & O Streets NW
    Washington DC 20057-1174
    202.687.7385
    digitalscholarship@georgetown.edu
    Accessibility