| Project title | Understanding How Epigenetic Abnormalities Lead to Brain Cancers |
|---|---|
Grant Amount | $200,000 |
Institution | Monash University |
Investigator Team | Principal investigators A/Prof. Lee Wong |
Grant Type | 2014 Innovation Grant |
Years | 2014 – 2017 |
Certain genes are known to be frequently mutated in brain cancers. These mutations are thought to be early events which drive the formation of tumours, and often include factors which are involved in genome regulation.
A/Prof. Lee Wong and her team have successfully recapitulated two of these genetic mutations in a cell model, effectively creating a pre-cancerous model of brain tumours. These mutations destabilised the genome of the pre-cancerous cells and led to the abnormal expression of normally silent genomic repeats. They have found widespread changes in genome organisation which is likely to contribute to the pathology of brain tumours.
This research project will reveal how genetic mutations trigger brain cancers. Further mutations can also be introduced into the pre-cancerous cells created in this study. These can then be differentiated into neural cells to fully recreate the early events in brain tumours. This will yield an accurate stage-by-stage cell model of brain cancers and allow researchers to better understand how these tumours form. These cell models could also be used for future drug screens and identify the therapies which would be most effective for particular combinations of brain cancer mutations.
“Outcomes from this work will provide insights into ALT mechanism in cancers and we could apply the knowledge to develop therapy against ALT in cancers, including brain cancers.”
A/Prof. Lee Wong
Progress
With the support from Cure Brain Cancer, we were able to generate cells with ATRX loss of function, which is closely linked to an abnormal chromosome structure phenotype called ALT (Alternative lengthening of telomeres) in human cancers, particularly brain cancers.
ALT is activated in 40% of brain cancers and these ALT cancers have >90% in ATRX mutations. ALT human cancers use a unique mechanism to lengthen the telomeres (structures that are essential for cell growth and survival).
The funding from Cure Brain Cancer has allowed us to create ATRX mutant cells. These ATRX-null cells are also being used for studying the mechanisms that suppress ALT activation to prevent cancer formation.
This work now is being funded by NHMRC (2017-2019). Without the funding from CBCF, we would not be able to generate important findings that could be used for grant application to NHMRC Australia.