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Histone deacetylases in paediatric glioblastoma

Student thesis: Doctoral Thesis

Paediatric glioblastoma multiforme (pGBM) is an aggressive childhood brain tumour with less than 10% of children surviving two years post diagnosis. There is no cure, and treatment options are limited and ineffective. Gene expression profiling, whole-exome sequencing and genome wide copy number analyses have revealed a number of ‘oncohistone’ mutations amongst pGBM. Acetylation and deacetylation of histones and non-histone proteins is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs, critical for development, are involved in modulating key cellular processes, including DNA damage repair, cell cycle control, apoptosis, transcriptional regulation and metabolism. Their functioning in cancer is impaired and the potential use of HDAC inhibitors for cancer treatment is an active area of both basic and clinical research. There are 11 HDAC family members, grouped according to their structure, cellular localization and homology with yeast HDAC proteins.
Little is known about HDAC expression in pGBM. The hypothesis for this study was that HDACs would be over-expressed in pGBM, given the wide use of HDACi research. The aims of this project were to; 1) systematically analyse HDAC expression in pGBM using publicly available datasets, 2) Begin to characterise HDAC expression in two, well-characterised paediatric GBM cell lines in order to identify specific HDAC family members that are dysregulated in pGBM.
Original languageEnglish
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Award date2017

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