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Identification of DNA methyltion changes in sporadic breast and other cancers

Hill, Victoria Kate (2011)
Ph.D. thesis, University of Birmingham.

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Abstract

Aberrant DNA methylation is a well known characteristic of cancer genomes. It can be used as a way of identifying important genes in tumourigenesis and can have diagnostic/prognostic value.

Using a genome-wide methylated DNA affinity enrichment approach this work identified five genes (DBC1, CIDE-A, EMILIN2, FBLN2 and SALL1) that are hypermethylated in sporadic breast cancer. Methylation of one of these genes, EMILIN2, was found to associate with worse disease free survival (DFS). A second genome wide approach assessing over 27,000 CpG loci was carried out on sporadic breast cancer patient samples and identified greater overall methylation in ER positive tumours and those that relapsed. Individual locus analysis identified six genes where methylation associated with worse DFS. Of these, promising candidates for further analysis were identified, including RECK, ACADL and C1orf114.

Candidate gene approaches also identified methylation of two newly characterised cancer-related genes, RASSF10 and KIBRA. Analysis of a range of solid cancers identified hypermethylation in multiple tumour types for RASSF10, the most frequent being gliomas. Frequent hypermethylation of KIBRA was identified in childhood acute lymphocytic leukaemia (ALL).

This study has used genome wide methods and candidate gene approaches to identify several novel methylated genes in a range of tumour types.

Type of Work:Ph.D. thesis.
Supervisor(s):Latif, Farida
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:R Medicine (General)
RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Institution:University of Birmingham
ID Code:2909
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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