Studying relationship between increased 5-methylcytosine oxidation and expression of cancer stem cell markers in glioblastoma cell lines

Wijeyagumar, Vithusha (2018) Studying relationship between increased 5-methylcytosine oxidation and expression of cancer stem cell markers in glioblastoma cell lines. MRes thesis, University of Nottingham.

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Abstract

DNA methylation (5-methylcytosine, 5mC) is an epigenetic modification generated by the addition of a methyl group to the 5 position on the cytosine ring of the DNA and it is important for a range of biological processes such as development and chromosome stability. 5mC can be enzymatically oxidised to 5-hydroxymethylcytosine, 5-fCformylcytosine and 5-carboxylcytosine (5caC) by TET proteins. These oxidised forms of 5mC may both serve as intermediates in the process of active DNA demethylation and/or contribute to the regulation of transcription. According to our results, 5caC exhibits heterogeneous distribution between different cells in glioblastomas (GBM), aggressive gliomas classified as grade IV astrocytoma which is always rapidly growing and highly malignant. Interestingly, GBMs are highly heterogeneous cancers containing a cancer stem cell (CSCs) subpopulation which is responsible for the reoccurrence of the tumour after treatment.

In the present study we examine the spatial distribution of 5caC in brain tumour cell lines and show that the levels of this modification positively correlate with the staining intensity of such CSCs markers as SOX2 and Olig2 in GBM cells. Our results imply that GBM CSCs may be enriched in 5caC and therefore, this oxidised form of 5mC may be employed for identification of stem cell-like populations in GBM with potential future implications for diagnostics and therapy of the brain tumours.

Item Type: Thesis (University of Nottingham only) (MRes)
Supervisors: Ruzov, Alexey
Keywords: DNA methylation; Brain tumour cell lines; Glioblastoma cells
Subjects: R Medicine > RC Internal medicine > RC 254 Neoplasms. Tumors. Oncology (including Cancer)
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID: 55512
Depositing User: Wijeyagumar, Vithusha
Date Deposited: 15 Apr 2019 12:06
Last Modified: 15 Apr 2019 12:06
URI: http://eprints.nottingham.ac.uk/id/eprint/55512

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