What is it about?
Diffuse midline glioma (DMG) is a deadly childhood brain tumor. Like many cancers, DMG is caused by mutations – that is, changes in our DNA. Remarkably, ~80% of all DMG tumors share the same “H3K27M” mutation, one that is rarely found in other diseases and whose cancer-causing roles are poorly understood. The main goal of our research was to understand how we can block the effects of H3K27M to help treat DMG. In conventional research models, only a few ways can be tested in a single experiment. We sought to remove this limitation in scale and created a laboratory model which allowed testing hundreds of millions of ways at the same time. Using this model, we discovered twenty ways (out of millions) to suppress H3K27M function. Some of these were previously known or expected, thus providing important validation for our model. However, some were unexpected; our most surprising discovery was that blocking a protein from modifying parts of chromosomes with a previously unstudied chemical modification prevented many effects caused by H3K27M. This finding may guide the development of new therapeutic strategies for DMGs.
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Photo by Sangharsh Lohakare on Unsplash
Why is it important?
Our discovery of ubc-20 mutations which suppress H3K27M phenotypes points to a new pathway which may be targeted for therapeutic benefit in pediatric gliomas.
Perspectives
I am very grateful for the ChadTough Defeat DIPG Foundation for supporting this work. I am hopeful that our findings will contribute to the development of new therapies for pediatric glioma patients.
Alan Jiao
University of Oxford
Read the Original
This page is a summary of: An E2 ubiquitin-conjugating enzyme links diubiquitinated H2B to H3K27M oncohistone function, Proceedings of the National Academy of Sciences, November 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2416614121.
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