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Title: Carcinoma of the cervix : molecular genetic analysis
Author: Busby-Earle, R. M. Camille
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1994
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RFLP analysis was used to detect loss of heterozygosity in tumour/blood pairs, from patients with cervical carcinoma, to examine the role of commonly implicated tumour suppressor genes in cervical carcinogenesis. Allele losses were detected less frequently than has been reported in many other common solid tumours. This relatively low level of allele loss was supported by the infrequent genetic alteration identified when comparison was made between tumour/blood DNA fingerprints from cervical carcinoma patients and those with cancers of non-cervical origin. No correlation was found between allele loss and HPV status when polymerase chain reaction (PCR) was used with DNA extracted from cervical carcinomas to detect HPV types commonly associated with genital lesions. The mutational status of p53 gene was examined in a series of cervical carcinomas by a method employing PCR and denaturing gradient gel electrophoresis, and comparisons were made between the HPV and p53 mutational status of these tumours. Mutation in p53 gene was detected relatively infrequently, and contrary to recent reports, was not commonly associated with HPV negative status. Mutations were characterised by sequencing. The use of p53 specific monoclonal antibodies in immunohistochemical analysis of normal, premalignant, and malignant cervical epithelium confirmed that p53 was seldom present in detectable quantities at any stage in the progression of this disease, and lent support to the finding of a low frequency of p53 mutations in this tumour type. Y13 259, a monoclonal antibody to ras p21 oncoprotein, used to compare ras expression at various stages in cervical carcinogenesis, identified differences in expression in the glandular, but not the squamous, component of malignant and non-malignant cervical epithelium.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available