Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.626092
Title: The role of brachyury in the pathogenesis of chordoma
Author: Pillay, N.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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Abstract:
Chordoma is a rare malignant tumour of bone, the molecular marker of which is the expression of the transcription factor T (also referred to as brachyury). Silencing of T induces growth arrest in chordoma cell lines; however its downstream genomic targets are unknown. In this thesis I have identified these targets with validation in human chordoma samples. This was achieved by using an integrated functional genomics approach involving shRNA-mediated brachyury knockdown, gene expression microarray, ChIP-seq experiments and bioinformatics analyses. The results show that T regulates a downstream network that involves key cell cycle related genes amongst other potential oncogenic programmes. This is the first documentation of genomic T targets in humans and provides a molecular insight into the pathogenesis of chordoma. In a separate but related piece of work, a genetic association study was conducted to determine the genetic susceptibility determinants in patients with sporadic chordomas. Whole-exome and Sanger sequencing of T exons revealed a strong risk association with the common non-synonymous SNP rs2305089 in chordoma. The degree of risk imparted by this variant is large and is an exceptional finding in cancer genetics. Overall the work presented in this thesis contributes to the evolving understanding of T’s role in the pathogenesis of this rare bone cancer.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.626092  DOI: Not available
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