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Title: Involvement of the WT1 and p16 genes in Wilms' tumour and human malignant mesothelioma
Author: Williamson, K. A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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WT1 identified as a gene repeatedly disrupted in Wilms' tumour, a common paediatric renal malignancy. This study is one of many which sought to confirm and understand some of the roles of WT1 in both normal development and tumorigenesis. Mutation analysis of WT1 in samples from patients with sporadic, bilateral and syndrome-associated Wilms' tumour has produced a pattern of results consistent with the findings of other groups. No mutations were detected in the sporadic and bilateral tumours, however exonic point mutations were detected in 7 out of 9 syndrome-associated Wilms' tumour samples that were analysed in detail. Studies examining parental WT1 status, genomic imprinting and allele loss distal to the WT1 locus are detailed for the syndrome-associated Wilms' tumour samples. p16 was identified not only as a cell cycle regulator, but also as a gene repeatedly deleted in tumour cell lines. Previous studies showed that tumours of various types, including primary malignant mesothelioma, often contain deletions spanning the p16 locus. In this study detailed deletion analysis is presented for p16 and the adjacent related gene, p15, in Wilms' tumour and malignant mesothelioma samples. Both primary tumours and tumour cell lines were analysed. Deletions of p16 were not detected in Wilms' tumour and derived tumour cell lines. Deletions of p16 were however detected in all malignant mesothelioma cell lines analysed, and in the majority of these (14 out of 15) the deletions extended to the p15 locus. Analysis of p16 and p15 in primary malignant mesothelioma samples did not identify deletions of either gene. The contribution, resulting effects and complementary nature of WT1 and p16 mutations in Wilms' tumour and malignant mesothelioma is discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available