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Title: The role of p53 in colorectal carcinogenesis
Author: Purdie, Colin Alexander
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1994
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Expression of p53 was studied immunohistochemically in a consecutive series of resected human colorectal tumours using monoclonal antibody PAb1801. Expression was detected in 41 of 87 carcinomas (47%) but in only 4 of 46 sporadic adenomas (8.7%) indicating that p53 expression is associated with malignant transition in colorectal tumourigenesis. Fine mapping of the deletion on chromosome 17p using 4 polymorphisms indicated allele loss in 46 of 79 cases (58%) and that this usually included the p53 gene locus. Loss of any 17p allele and loss of markers adjacent to or within the p53 gene correlated with p53 expression and thus mutation. There was also a correlation between 17p allele loss and the presence of DNA aneuploidy. Loss of a marker on chromosome 17q was seen in 13 of 64 (20%) of colorectal cancers. This is a higher frequency than detected previously and correlated in this series with the presence of lymph node metastasis suggesting the presence of a tumour metastasis suppressor gene at this locus. These results indicate a central role for p53 inactivation in human colorectal tumourigenesis probably at the critical phase of malignant transition, possibly by permitting premature replication or replication in the presence of DNA sequence abnormalities and the development of aneuploidy. Although not necessary for normal development in mice, p53 is vital in the prevention of carcinogenesis and p53 deficient mice will permit further study of cancer prevention and therapy. Finally, a possible tumour metastasis suppressor gene locus has been identified on chromosome 17q.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available