Methylated Circulating Tumour DNA in Myeloma
Chai, Yun Kern
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Cite this item:
Chai, Y. K. (2018). Methylated Circulating Tumour DNA in Myeloma (Thesis, Master of Medical Science). University of Otago. Retrieved from http://hdl.handle.net/10523/8550
Permanent link to OUR Archive version:
http://hdl.handle.net/10523/8550
Abstract:
Myeloma is an incurable malignancy of plasma cells in the bone marrow. Improvements in myeloma treatment have highlighted the need for more sensitive non-invasive measures of residual disease. Circulating tumour DNA in the plasma fulfils this need, but the use of mutation-based monitoring is limited by the vast genetic heterogeneity of myeloma, by the known clonal evolution of myeloma and the cost. To avoid these limitations, a novel approach using methylation differences to distinguish circulating myeloma DNA from healthy cell-free DNA was designed.
A final biomarker panel consisting of two differentially methylated genes (PPFIA1 and SLC9A3) was identified. This panel was measurable in more patients (84.4%) compared to conventional protein biomarkers (55%) or a targeted sequencing panel of the commonest genetic mutations (63-68%). Additional advantages of this novel circulating tumour DNA biomarker panel include a “real-time” representation of disease burden and being able to track clonal evolution. Based on a small number of cases, these methylation biomarkers reflect response to treatment, predict relapse earlier and potentially guide therapeutic choices. Follow up studies to validate these results are required.
Date:
2018
Advisor:
Morison, Ian; Pattison, Sharon; Weeks, Rob
Degree Name:
Master of Medical Science
Degree Discipline:
Pathology and Medicine (jointly hosted)
Publisher:
University of Otago
Keywords:
epigenetics; Methylation
Research Type:
Thesis
Languages:
English
Collections
- Thesis - Masters [3328]
- Pathology collection - Dunedin [78]
- Medicine - Dunedin [89]