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