Epstein-Barr virus-associated malignancies: Susceptibility factors and molecular detection in liquid biopsies

    Onderzoeksoutput: Thesis fully internal (DIV)

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    Epstein-Barr virus (EBV) infects >90% of the world’s population and leads to the development of Hodgkin lymphoma (HL) and nasopharyngeal carcinoma (NPC) in a low percentage of  individuals. In addition, uncontrolled growth of EBV infected B cells can cause post-transplant lymphoproliferative disorder {PTLD) in patients treated with immunosuppressive drugs following organ transplant. The main aims of this thesis are to explore i) risk factors of HL and NPC, and ii) biomarkers in NPC, HL and PTLD.
    Several human leukocyte antigen (HLA) alleles have been associated with susceptibility to HL and NPC. We identified novel NPC-associated HLA-alleles in the high-risk Bidayuh minority population from Malaysia. We also showed that loss or retention of HLA expression by tumor cells is associated with a subset of known protective or risk alleles in both HL and NPC. These data suggest that the susceptibility effects of HLA alleles are early events in pathogenesis, while the pressure on tumor cells to downregulate HLA is most likely related to emerging immune responses later on.
    With plasma or nasal washing derived EBV DNA, we could detect NPC disease activity with high sensitivity. Chromosomal copy number variations were detected in cell-free DNA of >50% of HL and PTLD patients. Targeted sequencing of EBV demonstrated 100% sensitivity in detecting disease in EBV-positive HL and PTLD patients. These findings suggest that measuring  cell-free biomarkers in liquid biopsies has clinical value in detecting disease activity in NPC, HL and PTLD.
    Originele taal-2English
    KwalificatieDoctor of Philosophy
    Toekennende instantie
    • Rijksuniversiteit Groningen
    • van den Berg, Anke, Supervisor
    • Diepstra, Arjan, Supervisor
    • Tan, Lu Ping, Co-supervisor
    Datum van toekenning1-nov-2021
    Plaats van publicatie[Groningen]
    StatusPublished - 2021

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