Author ORCID Identifier
Date of Graduation
Doctor of Philosophy (PhD)
Cancer-associated mortality has been declining for two decades but remains a significant public health problem, especially when patients initially present with advanced disease. Early detection methods have improved survival rates but remain unavailable for a majority of cancers due to a lack of sensitive biomarkers or numerous limitations associated with current diagnosis strategies. Approaches to develop “liquid biopsies” by detecting tumor cells or DNA in the blood have led to several breakthroughs and create the potential for non-invasive, routine assessment of diseases status. However, these biomarkers are rare and currently difficult to isolate, especially in the early stages of disease. Exosomes on the other hand, are phospholipid nanovesicles that reflect the molecular contents of their cell of origin and are abundantly present in bodily fluids. Due to this, exosomes have attracted considerable interest as a source for theranostic biomarkers, and may also be important participants of tumor progression. Here, we characterize exosomes and their DNA content (exoDNA) from human cell lines and bodily fluids to assess their utility as circulating biomarkers of disease. In addition, we explore the origins of exoDNA, as well as its delivery and transcriptional capacity in other cells. We found that exoDNA from cancer cell lines and serum and urine of patients with bladder cancer is encapsulated within exosomes and spans the entire genome. We also discovered unique somatic mutations in serum and urine exosomes that are absent in tumor tissue, and propose the use of urine exosomes for non-invasive biomarker detection in bladder cancer. Lastly, our results indicate that DNA-containing exosomes may be partly comprised of vesicles that evolve from the nuclear membrane and horizontally transfer DNA to recipient cells.
Exosomes, DNA, Pancreatic Cancer, Bladder Cancer, Biomarker, Sequencing