Monash researchers make key insight into brain cancer biology
Brain cancers kill more children than any other disease and more people under the age of 40 than any other cancer. A lack of understanding about how these cancers form and develop, and a lack of effective treatments for the most common and aggressive forms of them has meant that low survival rates have hardly changed in 30 years.
A study by Monash University Biomedicine Discovery Institute (BDI) researchers, published today in Nature Communications, has provided new insights into the biology of brain cancer, which may generate future knowledge underpinning treatments.
The study, led by Associate Professor Lee Wong, investigated brain cancer mutations in histone genes. Histone is a protein that packages and protects DNA from mutation and keeps stable the information it sends that ultimately affects cell growth and behaviour.
Mutations in histone genes have remained puzzling, despite being found across a number of different cancers, including paediatric brain cancers.
The researchers created a perfect copy of one of these histone H3.3 gene mutations in normal cells, to establish what it does to make them cancerous.
“We didn’t know how it would drive abnormal behaviour in the cells that cause cancer,” Associate Professor Wong said.
“We found that the brain cancer histone mutation blocks the action of an epigenetic eraser in the genome. The epigenetic eraser is a histone modifier and part of the network that regulates histone function and DNA processes,” she said.
“We’re quite excited, as we were able to use knowledge gained from gene sequencing on tumours. Now we can create a model to study the disease in a very fundamental way to give fundamental knowledge.”
“Our findings help to build a foundational understanding of the biology of brain cancer, and represents a crucial progression from identifying mutations to defining a function.”
Associate Professor Wong said the research provides a bridge to future work that could potentially translate this knowledge into treatments for brain cancer.
“We believe that unless we have a clear understanding of how a gene mutation (in this case histone gene mutation) works to destroy the genome organisation or epigenetic network, it is nearly impossible to develop new, accurate and effective therapeutic options,” she said.
“Understanding the basic biology of brain cancer and increasing our knowledge of the disease is a critical step in helping identify future treatments and improving brain cancer survival rates,” Michelle Stewart, CEO of Cure Brain Cancer Foundation, said.
“Cure Brain Cancer Foundation is proud to fund Associate Professor Wong’s work, and we look forward to future discoveries this knowledge can facilitate,” she said.
“The researchers would like to give sincere thanks to the Cure Brain Cancer Foundation and to our generous supporters – without this dedication and support, the pioneering projects we perform simply would not happen,” Associate Professor Wong said.
First author was Dr Hsiao Voon.
This research was supported by the Cure Brain Cancer Foundation. It also received funding from The Isabella and Marcus Paediatric Brainstem Tumour Fund and the Australian National Health and Medical Research Council. Associate Professor Wong is an Australian Research Council Future Fellow.
Read the full paper in Nature Communications, titled Inhibition of a K9/K36 demethylase by an H3.3 point mutation found in paediatric glioblastoma.
About the Monash Biomedicine Discovery Institute
Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.
About Cure Brain Cancer Foundation
Cure Brain Cancer Foundation is Australia’s leading organisation for brain cancer research, advocacy and awareness. Since the Foundation launched its mission in 2013 to increase brain cancer survival from 20% to 50% by 2023, the disease has gone from being a ‘forgotten cancer’ to a national health priority. Cure Brain Cancer Foundation has funded 34 research projects in 24 institutions, working with 250 collaborators across the globe. The Foundation currently funds five world-class clinical trials.