Characterisation of deregulated miRNA expression in paediatric brain tumours

Laura Genovesi

    Research output: ThesisDoctoral Thesis

    356 Downloads (Pure)

    Abstract

    [Truncated abstract] Introduction: Medulloblastoma (MB), the most common paediatric malignant brain tumour, is a heterogeneous disease consisting of several molecular sub-types with distinct clinical outcomes. Current risk stratification strategies divide patients into average-risk or high-risk treatment groups, which often fail to accurately account for the heterogeneity and consequent prognostic variability within the disease. Although overall survival rates for average-risk MB have recently improved, the outcome for high-risk patients remains poor. Additionally, the long term consequences of current treatment protocols remain significant. The development of less invasive targeted therapies for MB is hampered by an incomplete understanding of the pathogenesis of MB. Recent array-based genomic and transcriptomic analyses have contributed to an improved sub-classification of MB, identifying distinct molecular sub-types of MB defined by specific gene expression signatures and related clinical features. Identification of sub-type specific gene expression signatures may ultimately improve risk stratification strategies, contributing to a greater understanding of MB tumourigenesis and the development of more sub-type specific models of disease. Importantly, the identification of several molecular sub-types of MB suggests that each may arise from a distinct cell of origin. Indeed, murine and human studies have implicated CD133+ neural stem cells (NSCs) as candidate cells of origin for at least some sub-types of MB. However, the link between deregulated NSC growth and MB pathogenesis has not been formally proven, and the molecular mechanisms underlying the transformation of NSCs are poorly understood. Several research groups have investigated microRNA (miRNA) expression in MB relative to normal human adult and/or foetal cerebellum, which represent heterogeneous tissues at different developmental stages.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2011

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