Dissertation
TRANSCRIPTOMIC CHARACTERIZATION OF CANINE SOFT TISSUE SARCOMAS: SUBTYPE AND SURVIVAL ANALYSIS
Washington State University
Doctor of Philosophy (PhD), Washington State University
01/2022
DOI:
https://doi.org/10.7273/000004634
Handle:
https://hdl.handle.net/2376/125092
Abstract
Soft tissue sarcomas are a heterogenous group of mesenchymal cancers that include more than 80 histological subtypes. Soft tissue sarcomas make up less than one percent of all adult cancers and this rare occurrence, combined with their variable presentation, makes soft tissue sarcomas difficult to both diagnose and treat. In the past two decades, considerable effort has been put into improving care for soft tissue sarcoma patients with a focus being put on tailored treatment based on histological subtype. These efforts have been driven by advancements in technologies, such as next generation sequencing, that have allowed genetic and molecular characterization of individual soft tissue sarcoma subtypes. However, challenges remain in the development of new therapeutics. Due to the limited number of patients with soft tissue sarcomas, clinical trials often combine multiple subtypes thereby potentially diluting the detection of therapeutic activity. Pet dogs may provide an additional avenue for the discovery and testing of new therapeutics. Soft tissue sarcomas comprise 15% of all canine cancers. Along with the higher incidence, the use of dogs as a model provides additional benefits such as the cancers arising spontaneously in an intact immune system and exposure to similar environments as humans. However, much less is known about the genetic components of different canine soft tissue sarcoma subtypes. This dissertation attempts to provide insight by performing transcriptomic analysis on the three most common canine soft tissue sarcoma histotypes. First, we show that it is possible to get robust sequencing data from archived canine soft tissue sarcoma samples and that the gene expression profiles of canine soft tissue sarcoma tumors can be used, in conjunction with histology, to provide a more accurate subtype diagnosis. Second, we identify potential transcription factors whose dysregulation may lead to tumorigenesis of canine soft tissue sarcomas in general as well as development of each subtype. Lastly, we identify potential drivers of patient survival in canine soft tissue sarcomas. Together, our data highlights potential drivers of canine soft tissue sarcoma as well as what differences in gene expression may drive the formation and behavior of one subtype versus another.
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Details
- Title
- TRANSCRIPTOMIC CHARACTERIZATION OF CANINE SOFT TISSUE SARCOMAS
- Creators
- Lydia Lam
- Contributors
- Eric A Shelden (Advisor)Clifford E Berkman (Committee Member)Margaret E Black (Committee Member)Patricia A Hunt (Committee Member)Jill L Johnson (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Molecular Biosciences, School of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 119
- Identifiers
- OCLC#: 1365772532; 99900898638501842
- Language
- English
- Resource Type
- Dissertation