Bushell, Kevin Reid - Applications of next-generation sequencing to canine B-cell lymphoma and detecting ctDNA in solid hu...

This thesis has been approved for inclusion in the SFU Library.
Publication of this thesis has been postponed at the author's request until 2017-12-22.
Term: 
Fall 2016
Degree: 
M.Sc.
Degree type: 
Thesis
Department: 
Department of Molecular Biology and Biochemistry
Faculty: 
Science
Senior supervisor: 
Ryan Morin
Publishing Documentation
Postponement release date: 
Fri, 2017-12-22
Thesis title: 
Applications of next-generation sequencing to canine B-cell lymphoma and detecting ctDNA in solid human cancers
Given Names: 
Kevin Reid
Surname: 
Bushell
Abstract: 
Next-generation sequencing (NGS) has driven progress on diverse fronts in cancer research. We explored the utility of a highly-multiplexed, sensitive NGS-based method for the detection of circulating tumour DNA (ctDNA) and applied it to numerous human cancers. We used this method to detect clinically relevant mutations in a high proportion of advanced melanoma, lung, and colorectal cancer cases. We detected ctDNA in pancreatic ductal adenocarcinoma patients before and after resection and show that detection of ctDNA after surgery is a marker of poor prognosis. We also applied a combination of global and targeted sequencing to identify recurrent genetic events underlying canine B-cell lymphoma (cBCL). We report frequent mutations that inactivate TRAF3 and deregulate MYC stability. Both represent potential commonalities between cBCL and human non-Hodgkin lymphomas and support the use of cBCL as a clinical model of these diseases. These findings may also lead to improvements in treating cBCL.
Keywords: 
Cancer; Genetics; Next-generation sequencing; circulating tumour DNA; Biomarkers; Canine lymphoma
Total pages: 
143