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dc.contributor.authorYeh, Paul Sung-Hao
dc.date.accessioned2018-11-07T04:16:52Z
dc.date.available2018-11-07T04:16:52Z
dc.date.issued2018en_US
dc.identifier.urihttp://hdl.handle.net/11343/217352
dc.description© 2018 Dr. Paul Sung-Hao Yeh
dc.description.abstractAdvances in genomic sequencing have improved clinical outcomes in patients with haematological malignancies by allowing more refined diagnostic and prognostic stratification. However, significant challenges still remain due to tumour heterogeneity and the development of treatment resistance. Capturing serial genomic information in patients is important to not only understand the molecular mechanisms behind therapy response or resistance, but will also guide future therapeutic strategies. However, obtaining adequate and representative tissue for molecular analysis is often challenging and unfeasible due to the invasive nature of tissue biopsy. This work has utilised cell-free circulating tumour DNA (ctDNA) as a minimally invasive means to provide molecular information in patients undergoing therapy in chronic lymphocytic leukaemia (CLL) and myelodysplastic syndrome (MDS). Using a suite of sequencing technologies, this work has shown the feasibility and ability of ctDNA to detect various genomic lesions associated with disease. Additionally, serial analysis of ctDNA has been able to accurately monitor disease during therapy, and in some cases, circumvents issues encountered with current disease monitoring strategies. Finally, ctDNA analysis has also been shown to predict impending treatment failure and demonstrate clonal evolution highlighting the potential as a molecular biomarker. This provides a platform for future research to refine the use of ctDNA as a disease monitoring strategy. This thesis has also developed a methodology to simultaneously interrogate multiple genes simultaneously at high sensitivity. This has subsequently been used to successfully detect clonal haematopoiesis in allogeneic stem cell transplant donors and acute myeloid leukemia (AML) patients in complete remission. Although in these cohorts, individuals do not have an active haematological disorder, there appears to be an increased detection rate of sub-clinical mutations compared to what may be expected in the literature and provide a rationale for future work to determine the impact of these genetic lesions in the development of haematological malignancies.en_US
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dc.subjectmolecularen_US
dc.subjectctDNAen_US
dc.subjectmyelodysplastic syndromeen_US
dc.subjectchronic lymphocytic leukaemiaen_US
dc.titleMolecular monitoring and screening in haematological malignanciesen_US
dc.typePhD thesisen_US
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.thesis.supervisornameDawson, Mark
melbourne.contributor.authorYeh, Paul Sung-Hao
melbourne.accessrightsThis item is embargoed and will be available on 2020-11-07.


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