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Reason: Under embargo until 27 February 2024. After this date a copy can be supplied under Section 51(2) of the Australian Copyright Act 1968 by submitting a document delivery request through your library.
A Functional genomics approach to identify new therapeutic targets in DIPG
thesis
posted on 2023-02-16, 01:13 authored by MOTAHHAREH TOURCHI ROUDSARIDiffuse intrinsic pontine glioma (DIPG) is an aggressive paediatric brain tumour that is incurable. H3K27 methylation is catalysed by PRC2 via EZH1/EZH2. We show that EZH1 partially compensates for EZH2 loss in DIPG cells. Dual targeting of EZH1/EZH2 inhibits proliferation of DIPG cells and reduces H3K27me3 more effectively than selective targeting of EZH2. H3K27M mutations affected H3K27me3 distribution and DIPG cell proliferation directly. Furthermore, EZH1/EZH2 and H3K27M alter gene expression. The work presented here has identified several potential combinations that act by altering abnormal trimethylation levels. Taken together, we revealed a therapeutic vulnerability that can be targeted using combination therapies.
