Towards the molecular diagnosis of bladder and colorectal cancer : Analysis of CD44 exon splicing

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dc.contributor.advisorWoodman, Anthony C.
dc.contributor.authorMorgan, Sarah Louise
dc.date.accessioned2023-04-20T15:11:23Z
dc.date.available2023-04-20T15:11:23Z
dc.date.issued2002-08
dc.description.abstractThe literature suggests that CD44 has the potential to be used as a non-invasive tumour specific marker for early detection and monitoring. The gene transcript can undergo alternative splicing, leading to the production of a number of isoforms and it has been noted that in neoplastic states this splicing becomes abberant, leading to the production of a number o f variant isoforms. The aim of this study was to analyse CD44 variant expression with the goal o f reaching a platform from which a non- invasive assay for routine clinical use could be produced. In this study, the analysis o f exon junction splicing in bladder cancer has also led to the finding of a tumour specific junction expressed in 64% o f tumours studied. This exon junction (5/11) was found to be the same as that expressed in colorectal cancer. Though mRNA based assays would provide a satisfactory method for exon junction identification, a protein based approach would provide the platform for a more robust assay. Translation of gene expression data led to the design of a short synthetic peptide which overlapped the 5/11 junction, and this was used to produce a novel polyclonal antibody for this transitional epitope. The resulting polyclonal antibody was affinity purified and used in a pilot study of 5/11 expression in bladder and colorectal tumours. In bladder tumours the antibody demonstrated an overall specificity o f 76.5% and an overal sensitivity of 73.1 %, comparable to current commercially available early detection assays. In a Dukes staged colorectal cancer study, no link between stage and grade was noted, but the antibody gave an overall specificity of 76%. Though further analysis is required, it is thought the 5/11 antibody may prove to be a useful tool in the development o f a sensitive and specific assay for the non-invasive detection of bladder and colorectal cancer.en_UK
dc.description.coursenamePhDen_UK
dc.identifier.urihttps://dspace.lib.cranfield.ac.uk/handle/1826/19538
dc.language.isoenen_UK
dc.rights© Cranfield University, 2015. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.
dc.titleTowards the molecular diagnosis of bladder and colorectal cancer : Analysis of CD44 exon splicingen_UK
dc.typeThesisen_UK

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