DIPG is an aggressive type of brain tumour that originates in the pons, which is a part of the brainstem. The brainstem is responsible for vital functions such as breathing, heart rate, and consciousness, so tumours in this area can be particularly difficult to treat. Dr. Sanguino’s research aims to gain new information on how cancerous cells are formed through the mutation of histones (proteins that regulate the activity of genes). 

In the second year of her fellowship, Dr. Sanguino and her team identified the top six epigenetic changes associated with the presence of H3K27M mutation, the main cancer-causing aberration in DIPG, which includes H2A.Z acetylation, the focus of this project. They developed a protocol to understand the composition of onconucleosomes, defined as the nucleosomes, or basic units that pack the DNA, where the normal protein H3 is replaced by the mutant protein H3K27M.

For the first time, they have confirmed that these onconucleosomes also have H2A.Zac. Moreover, they have identified a targetable epigenetic vulnerability in DIPG, the enzyme p300. In vitro assays showed that blocking of p300 reduced growth of H3K27M+ DIPG cells. Together, this promising data has opened a new avenue for epigenetic treatment in DIPG, and it is hoped that further pre-clinical data will support the translation of this approach into the clinic.