• Admin Login
    View Item 
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of WIRECommunitiesTitleAuthorsIssue DateSubmit DateSubjectsTypesJournalDepartmentPublisherThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsTypesJournalDepartmentPublisher

    Administrators

    Admin Login

    Local Links

    AboutThe University LibraryOpen Access Publications PolicyDeposit LicenceCOREWIRE Copyright and Reuse Information

    Statistics

    Display statistics

    Characterisation of genetic and epigenetic aberrations in paediatric high grade glioma

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    CHANNATHODIYIL_PhD Thesis.pdf
    Size:
    8.448Mb
    Format:
    PDF
    Download
    Average rating
     
       votes
    Cast your vote
    You can rate an item by clicking the amount of stars they wish to award to this item. When enough users have cast their vote on this item, the average rating will also be shown.
    Star rating
     
    Your vote was cast
    Thank you for your feedback
    Authors
    Channathodiyil, Prasanna
    Issue Date
    2016
    
    Metadata
    Show full item record
    Abstract
    Paediatric high grade glioma (HGG), including diffuse intrinsic pontine glioma (DIPG) are highly aggressive tumours with no effective cures. Lack of understanding of the molecular biology of these tumours, in part due to lack of well-characterised pre-clinical models, is a great challenge in the development of novel therapies. Analysis of paired cell culture/biopsy samples in this study revealed that paediatric HGG short-term cell cultures retain many of the tumour characteristics in vivo. Using a genome-wide approach, copy number, gene and miRNA expression, and methylation changes were characterised in 17 paediatric HGG-derived short-term cell cultures including 3 from DIPG. The majority of the genomic changes were unique from those arising in adult HGG. Approximately 65% (11/17) of paediatric HGG short-term cell cultures had balanced genetic profiles resembling normal karyotypes. The most frequent copy number gain and loss were detected at 14q11.2 (94%) and 8p11.23-p11.22 (59%), respectively. H3F3A (K27M) mutation was present in 2/17 (12%) cases and concurrent loss of CDKN2A and BRAFV600E in 1/17 (6%) case. Genes involved in reelin/PI3K signaling (DAB1), RTK signaling (PTPRE), and arginine biosynthesis (ASS1 and ASL) were frequently deregulated by methylation in these tumours. The anti-growth and anti-migratory properties of DAB1 and PTPRE were demonstrated in vitro. Preliminary investigations validated the therapeutic potential of ADI-PEG20 (arginine depletion), and PI-103 (PI3K/mTOR inhibition) in a subset of paediatric HGG short-term cell cultures. This study has identified novel genetic and epigenetic changes in paediatric HGG that may, following further validation, be translated into potential biomarkers and/or therapeutic targets.
    URI
    http://hdl.handle.net/2436/617784
    Type
    Thesis or dissertation
    Language
    en
    Description
    A thesis submitted in fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of Philosophy.
    Collections
    Theses and Dissertations

    entitlement

     

    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.