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Title: The genetic basis of carcinogenesis in the clam enterocystoplasty
Author: Ivil, Kenneth Douglas
ISNI:       0000 0004 2672 0591
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2007
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The incidence of carcinoma following enterocystoplasty increases with time and there is an urgent requirement to develop techniques that can identify patients who will develop a life-threatening tumour. Endoscopic biopsies were taken from the ileovesical anastomosis and native bladder remnant (control specimens) of patients who had undergone a clam ileocystoplasty. Fluorescence in-situ hybridisation (FISH), using centromeric probes for chromosomes 8, 9 and 18, was performed on touch sample preparations from biopsies obtained from fifteen patients. Significant aneuploid changes were found at the ileovesical anastomosis in all cases. Chromosome 18 aneuploidy was present in thirteen patients and may prove to be a useful marker of anastomotic instability. FISH was also used to study tissue from a squamous cell clam cancer and demonstrated a large number of polyploid cells (twenty-three percent). A 'silent' p53 point mutation was identified at codon 192 by sequencing deoxyribonucleic acid (DNA) from this tumour. The restriction site mutation (RSM) assay was used to identify rare p53 mutations in DNA extracted from biopsies obtained from thirty-eight patients. The RSM assay studied five known hotspots for mutations of the p53 gene using the restriction enzymes Hha 1 (codon 175), Taq I (codon 213), Hae III (codon 249/250) and Msp I (codons 148 and 282). Early p53 mutations were found at the ileovesical anastomosis at codon 213 (one patient), codon 248 (three patients) and codon 250 (three patients). The mutations were characterised by sequencing the undigested, mutated polymerase chain reaction products obtained by RSM analysis. The anastomosis of patients who have undergone a clam ileocystoplasty is inherently genetically unstable and therefore prone to cancer formation. Both FISH and the RSM assay show promise as screening techniques and may prove to be useful in identifying those patients most at risk of developing a life-threatening tumour.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available