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Title: Identification of epigenetically dysregulated genes in tumours that metastasise to the brain
Author: Pangeni, Rajendra Prasad
ISNI:       0000 0004 7658 3062
Awarding Body: University of Wolverhampton
Current Institution: University of Wolverhampton
Date of Award: 2015
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Tumour metastasis to the brain is a common and deadly development in certain cancers; 18-30% of breast tumours metastasise to the brain. The contribution that gene silencing through epigenetic mechanisms plays in metastasis to the brain is not well understood. To identify epigenetic drivers of brain metastasis, a combined candidate gene screen using literature review, bioinformatics analysis of 450K methylation data of primary breast tumours from The Cancer Genome Atlas (TCGA) and Genome-wide methylation analysis of metastatic brain tumors that originated from primary breast tumours were carried out. A candidate gene approach identified two genes (BNC1 and CCDC8) dysregulated in breast to brain metastases (BBM) from a screen of 78 genes. Similarly, bioinformatic analyses of TCGA data identified GALNT9 and an independent comparison of genomewide methylation profiles in brain metastases identified 7 genes including non-coding RNA genes dysregulated in BBM. Taken together, these 10 genes identified are metastatic suppressor or promoter genes, which include novel regulatory elements noncoding RNA (ncRNAs) genes such as microRNAs, long intergenic non-coding RNAs (lincRNAs) or non-protein coding genes such as pseudogenes derived from their parental gene. Methylation analyses in BBM and their associated primary tumours from individual patients have revealed that identified genes are dysregulated either early or late in tumour evolution due to aberration in DNA methylation. In addition, methylation status of these genes in BBM correlates to serum DNA methylation in individual patients, which suggests that these genes could be used as a panel of prognostic markers or as therapeutic targets for BBM.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available