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
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/10822/1064766Date Published
2021Subject
Type
Publisher
Georgetown University
Extent
325 leaves
Metadata
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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
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 ...