Researchers working on deadly brain tumours mainly affecting children – diffuse midline gliomas (DMG) – have identified a potential new therapeutic strategy for the treatment of these currently incurable cancers.

A collaboration between Children’s Cancer Institute and the University of Sydney, published in the international journal Cell Death & Disease, the study focused on a new area of biology which until now has been largely unexplored in DMG, known as epi-transcriptomics.

This deals with chemical modifications made to the mRNA in a cell, which affect how the cell’s genes are expressed (switched on and off) and therefore how the cell behaves. Because these chemical changes are reversible, they offer an emerging opportunity for therapeutic intervention.

"This is the first time the epi-transcriptome has been investigated in DMG," said Dr Holly Holliday, Senior Research Officer, Brain Tumour Group at Children’s Cancer Institute, and co-first author on the study. "Epigenetic modifications to DNA are well known to play a crucial role in cancer, but this discovery shows that modifications to mRNA may also be very important."

Co-lead author Dr Samuel Ross, a postdoctoral researcher in the School of Life and Environmental Sciences at the University of Sydney said: "This is the first time RNA modifications have been explored in DMG, and we’ve found they’re crucial for the survival of these cancer cells.

"Because RNA modifications can be regulated in many different ways in the cell, these findings open up a number of new avenues for developing potential treatments."

Using cells derived from children with DMG and grown in the laboratory, the researchers studied a common mRNA modification, known as RNA N6-methyladenosine (m6A), finding that levels of m6A in the children’s DMG cells were significantly higher than in their normal cells. In particular, m6A levels were high in mRNA that helps the cancer cell infiltrate the normal brain tissue. These findings strongly suggest that m6A plays a critical role in the formation of DMG tumours.

The researchers were also able to show that DMG cells were sensitive to a type of treatment called FTO inhibition, with treated DMG cultures showing significantly decreased growth as well as reduced cell survival.

"These findings not only advance our understanding of DMG, highlighting mRNA methylation for the first time as a critical regulator of DMG tumorigenicity, but very importantly they also identify new therapeutic targets," said Professor David Ziegler, Group Leader of the Brain Tumour Group at Children’s Cancer Institute, Senior Specialist in the Kids Cancer Centre at Sydney Children’s Hospital, and co-senior author on the study.

"With further work yielding similarly promising results, this could ultimately lead to a new treatment for this cancer, which is desperately needed."

Professor Marcel Dinger, Dean of Science at the University of Sydney and joint corresponding author, said: "This study is a great example of what can happen when disease-focused expertise and genomics come together. 

"From the University of Sydney side, we were excited to help bring advanced RNA analysis into a very challenging childhood cancer, and to work with colleagues at Children’s Cancer Institute to uncover a new layer of biology that may point to future therapeutic opportunities.”

Research

Ross, S. et al 'RNA N6-methyladenosine (m6A) regulates cell cycle progression in diffuse midline glioma (DMG) and confers sensitivity to FTO inhibition' (Cell Death & Disease 2026). DOI: 10.1038/s41419-026-08647-8

Declaration

David Ziegler from Children's Cancer Institute reports consulting and advisory board fees from Novartis, Norgine and Medison Pharma and research support from Accendatech. The other authors declare no competing interests.

Funding was provided by the School of Biotechnology UNSW (ECR seed grant) and Ramaciotti Center for Genomics (medECAN seed grant). Samuel Ross was supported by a Cancer Institute of NSW Fellowship. Holly Holiday was supported by a Cancer Institute of NSW Fellowship and by the CanToo Foundation. David Ziegler is supported by grants from the National Health and Medical Research Council and Cancer Institute New South Wales Program Grant. Maria Tsoli is also supported by Levi’s Project. Mahdi Zeraati was supported by a Cancer Institute of NSW Fellowship.