DIPG

Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumour, most prevalent in young children and highly invasive in the surrounding tissue. With a mean survival time of 9 months post diagnosis, these inoperable tumours pose a major challenge in treatment, with the standard of care treatment yielding single digit survivability percentages.

Biologically, most DIPG tumours harbour mutations in histone 3 (H3), where a lysine-to-methionine substitution (K27M) is found. This mutation has been shown to drastically alter the general epigenetic landscape within the tumours, with a general decrease in repressive histone marks (H3K27me3) and increase in stimulating enhancer marks H3K27Ac. This global shift in expression patterns involves changes in cancer-related genes, ultimately driving cancer development, growth and invasion into the surrounding tissue.

Research into DIPG has been hampered by the nature of the disease; patient samples are rare, and both mice and cancer cell lines bring their own challenges with them, especially with regards to translation back into the human system. We have, in cooperation with our partners at the University of Michigan and Motts children's hospital, collected a range of primary human samples; we employ a multiplexed MINT-ChIP approach in combination with bulk RNA-seq to investigate the epigenetic and transcriptional state of these tumours, with a special focus on the differences in H3K27M mutations and intra-tumour heterogeneity.