Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.605236
Title: Biomarkers of prognosis and response to vitamin D in cutaneous melanoma
Author: Filia, Anastasia
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2013
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Abstract:
This thesis describes an evaluation of next generation sequencing (NGS) as a tool to study melanoma genomics and identify prognostic biomarkers using formalinfixed paraffin-embedded (FFPE) primary tumours. I report the evaluation of different library preparation protocols as a pre-requisite for whole-genome DNA NGS. I show that libraries can be generated using small amounts of DNA extracted from primary melanomas (92% success rate). NGS data from 75 samples are presented. To ensure the accuracy of the data and in order to develop a robust protocol for copy number analysis using small FFPE tumours the quality of the data was assessed and potential biases were explored. I observed copy number changes previously reported in melanoma which provide some support of the validity of the data when small DNA input is used. Although, this is work under development, overall the data show that NGS using small FFPE tumours is likely to provide insight into melanoma biology. I report a study where osteopontin was tested as a potential prognostic biomarker in the plasma of patients with melanoma. The analysis suggests that measurement of plasma osteopontin is unlikely to serve as a useful blood prognostic marker in earlystage disease patients, but it remains a possible marker of relapse in patients under follow up as part of a panel of such markers. The Leeds group have reported that low vitamin D levels at diagnosis are associated with thicker tumours and poorer outcome. I report an in vitro study where melanoma cells were cultured with and without vitamin D. Whole-genome gene expression data were generated using RNA from two vitamin D sensitive melanoma cell lines. The differentially expressed genes in response to vitamin D supported the anti-tumour effects of vitamin D previously reported in cancer models, providing some evidence for vitamin D as a potential adjuvant therapy.
Supervisor: Newton-Bishop, Julia ; Bishop, Tim ; Harland, Mark Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.605236  DOI: Not available
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