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A genetic mutation causing DMG and a potential drug to treat it

Geneticists from Trinity College Dublin have discovered how a specific genetic mutation called H3K27M causes a devastating, incurable childhood cancer, known as diffuse midline glioma (DMG), and, in lab studies working with model cell types, successfully reverse its effects to slow cancer cell growth with a targeted drug.

The top line:

Dr Adrian Bracken, at Trinity College Dublin, has just shared the results of a three-year project with the scientific community. He focused the work on a group of brain tumours called diffuse midline gliomas or DMGs (including the tumour type formerly known as DIPG). He and his team have shown that a genetic mutation called H3K27M causes lab cells to act like DMG, additionally he’s found a drug that reverses these effects and slows cell growth.

“These discoveries into an often inoperable brain tumour type are invigorating. Finding a cause and a potential treatment within one project is an amazing achievement. Our researchers bring new hope to families of children with DMG, and it's so desperately needed because a cure can't wait.” Says Dr Becky Birch, our Head of Research. “This research is also a great example of how collaborating with another funder, Worldwide Cancer Research, has paid dividends for our community.”

More detail:

A key factor in targeting drugs to brain tumours is knowing why they start in the first place. Geneticists from Trinity College Dublin have discovered how a specific genetic mutation called H3K27M causes DMG, and – in lab studies working with model cell types – successfully reverse its effects to slow cancer cell growth with a targeted drug.

Their landmark work – just published in leading international journal, Nature Genetics – translates crucial new understanding of the genetics of DMG progression into a promising, targeted therapeutic approach, and offers hope of improved treatments in the future.

The lab work has highlighted the effectiveness of an already approved class of drugs called “EZH2 inhibitors”. Crucially, these drugs have already received approval from the United States Food and Drug Administration (FDA) for the treatment of two types of adult cancer, lymphoma and sarcoma. This is great news for the potential of future DMG clinical trials, but we acknowledge that there is still work to be done before children with DMG are given these drugs.

Dr Bracken will continue with this work by searching for ways to make EZH2 inhibitors more effective against DMG, and to deepen our understanding of how H3K27M alters normal biology to promote tumour development.

Ultimately, we hope that our work – together with that of others focused in this area – will lead to curative clinical approaches for what is a truly terrible disease that can devastate families and for which there are currently no therapeutic options.

Dr Adrian Bracken - Associate Professor, Trinity College Dublin

The key findings and implications of this work are

  • How a specific genetic mutation called H3K27M causes DMG
  • How to target this cancer-causing gene with a drug that slows cancer cell growth
  • They have also established a specific model cell line for evaluating further targeted DMG approaches

Read more about the project we funded that led to these findings here. If you have any questions about this research, or other research we fund please contact us on research@thebraintumourcharity.org

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