Jafri, Mariam (2016). Molecular characterisation of renal cell carcinoma and related disorders. University of Birmingham. Ph.D.
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Jafri16PhD.pdf
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Abstract
Over the last two decades genetic advances have provided novel insights into the molecular basis of familial and sporadic cancers and provided the basis for the development of novel therapeutic approaches. For example, the identification of the gene for von Hippel Lindau disease provided seminal insights into its role in most clear cell renal carcinomas (RCC) and led to new treatments for RCC.
In this thesis I investigated three related genetic aspects of neoplasia. Firstly, I analyzed the results of genetic testing for inherited phaeochromocytoma and investigated how clinical features could be used to stratify patients and improve the cost effectiveness of genetic testing. Secondly, I sought to identify novel causes of inherited neoplasia. Through exome sequencing of familial RCC kindreds, CDKN2B was identified as a novel familial RCC gene. The role of CDKN2B mutations in neoplasia was evaluated in familial and sporadic RCC and phaeochromocytoma. In vitro assays confirmed that germline CDKN2B mutations associated with inherited RCC caused an abrogation of tumour suppressor function. Finally, I explored how a gene-based strategy might be used to identify novel therapeutic strategies, Thus, using a siRNA library screen, in RCC cells with inactivated VHL, potential candidate targets (e.g. PLK1/STK-10) were identified for selectively decreasing the viability of RCC cells with inactivated VHL.
Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
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Award Type: | Doctorates > Ph.D. | |||||||||
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College/Faculty: | Colleges (2008 onwards) > College of Medical & Dental Sciences | |||||||||
School or Department: | School of Clinical and Experimental Medicine | |||||||||
Funders: | None/not applicable | |||||||||
Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | |||||||||
URI: | http://etheses.bham.ac.uk/id/eprint/6996 |
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