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Title: Analysis of genetic changes in Barrett's oesophagus
Author: Croft, J. D.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 2001
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The work presented in this thesis involves the development and optimization of methods to analyze genetic changes for use on both fresh and archival material to study Barrett's Oesophagus. Comparative Genome Hybridization (CGH) was used to characterise genome wide changes that occur during the progression of Barrett's metaplasia through low and high-grade dysplasia to adenocarcinoma. In addition, interphase FISH using centromeric probes for specific chromosomes was used at each stage of the condition in an attempt to identify any increase in aneuploidy and genome instability consistent with progression. Finally, quantitative PCR was used to study the loss of heterozygosity of exon 6 of the p53 gene in all the high-grade samples that had already undergone analysis by CGH. The data demonstrates that high grade dysplasia is a stage of substantial karyotypic instability, with the amplification of 4q present in 60% of samples. By contrast, adenocarcinomas show less widespread chromosome changes with amplification of chromosome 8q being the most common feature. Aneuploidy was detected and increased with neoplastic progression. The presence of p53 mutations was also detected in 3 of the samples. Following the successful development and optimization of CGH it was decided to test its effectiveness further by using it to study colorectal cancer, to see if CGH confirmed the findings of other researchers. The results are consistent with previous findings and in addition, identify chromosome 16 as an area of high instability through each stage of colorectal cancer.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available