Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.640122
Title: Genomic instability, deregulation of apoptosis and treatment responsiveness in sporadic colorectal cancer
Author: Abdel-Rahman, W. M.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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Abstract:
Chromosomal instability was studied in 17 colorectal cancer cell lines using Spectral Karyotyping (SKY). RER-lines usually displayed extensive numerical and structural variations with marked heterogeneity. Most RER-lines showed a tendency to approach a near-triploid karyotype, and invariably had structural chromosomal changes including unbalanced translocations. Marked clonal heterogeneity was observed among cells of the same tumour line. Evidence of endoreduplication was much less frequent in these colorectal cancer cells than for other cancers reported in the literature. A minor subgroup of RER-lines retained a near-diploid karyotype, but displayed the same pattern of structural rearrangements and heterogeneity observed in the near-triploid pattern. Chromosomal gains and losses were in broad agreement with previously published data on primary cancers, indicating that the patterns observed in these cell lines are likely to be representative of primary colorectal cancers. In contrast, RER+ lines usually showed stability of both chromosome number and structure. p53 mutations were present in some of these RER+ lines, but were not associated with aneuploid karyotypes. Extensive chromosomal instability was identified in 3 out of 8 RER+ lines, one of which showed a near-triploid pattern as commonly seen in RER-tumours. Two RER+ lines were near-diploid and showed a striking and previously unreported tendency to acquire balanced translocations. Potential mechanisms underlying these different patterns of genomic instability are discussed. Bax gene mutations were detected in 50% of RER+ sporadic colorectal cancers, but were not always present at all tumour sites and hence must sometimes have arisen during tumour progression rather than in the founder clone. In contrast, TGFbRII mutations were found in 75% of the RER+ cancers, and were present in all the sampled sites: these mutations must have arisen in the founder clone. RER+ and RER- cancers were screened for mutations in the whole coding sequence of Fas and in a trinucleotide repeat tract identified in Bik, but no mutations were found in either.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.640122  DOI: Not available
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