Year: 2017
Type: dissertation
Abstract: Brain tumours are the most common solid tumours in children, with pediatric high-grade gliomas (PHGG) displaying clinically aggressive behaviour and dire survival outcomes. Previous evidence points toward a histone 3 variant H3F3A mutation (H3.3-G34R) in pediatric glioblastomas, which results in redistribution of the histone mark H3K36me3. It has been shown that H3K36me3 is necessary for recruitment of the mismatch repair (MMR) protein complex hMutSalpha (hMSH2-hMSH6). In vitro, Western blot and immunofluorescence analysis was performed on immortalized normal human astrocytes (iNHAs) to establish decreased H3K36me3 levels in S phase synchronized H3.3-G34R mutant cells. MSH6 foci formation was unaffected in the absence of a DNA damage inducing agent. In vivo, immunohistochemical analysis on H3.3-G34R xenograft tumour showed decreased levels of H3K36me3. Therefore, the H3.3-G34R mutation leads to loss of H3K36me3 levels, highlighting another impact of epigenetic disruption in PHGG.
Source: TSpace (University of Toronto)
Author: Stephie Leung
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2747147262