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Title: Identification and functional characterisation of germ line genes in human cancer cells
Author: Aldeailej, Ibrahim
Awarding Body: Prifysgol Bangor University
Current Institution: Bangor University
Date of Award: 2013
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Cancer is a leading cause of death worldwide and this is at least in part due to limitations in current therapies and late diagnosis. Thus, improving the tools to diagnose cancer at early stages and the development of new therapeutic targets is essential. One group of proteins that might be helpful for both diagnosis and immunotherapy targeting is known as the cancer/testis antigens (CTAs). CTA genes are expressed in the normal testis and should not be expressed in other healthy somatic cells, however these genes are expressed in various cancer cells. Therefore, identifying new bona fide CT A genes has great clinical importance. In this study, different strategies were used to identify and characterise new CT A genes. The results presented here identified eleven candidate CT A genes. Two CTA genes, SP011 and PRDM9 were validated at the protein level. SPO1l and PRDM9 proteins were detected only in the normal testis and not in any other normal tissues. PRDM9 was detected in different types of cancer and SPO1l was detected in all the cancer cell lines and most of the cancer tissues which were used in this study. These results suggest that SPO1l might be essential for the cancer cells. SPO1l was also found to be associated with the DNA, which might indicate that SPO 11 was bound to the DNA, giving rise to the possibility of DSB formation in cancer cells. The presence of SPOIl during mitotic cell division might lead to incorrect replication or/and formation of DSBs during mitosis, which might lead to different chromosome rearrangements and ultimately to cancer, suggesting that SPO1l could be an oncogenic driver. Therefore, defects in SPO 11 might cause cancer cells to undergo apoptosis, which might explain the level of cell death observed after the cancer cells were treated with siRNA and TALENs.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available