Lead investigator: Dr Keith Brown, University of Bristol
Funded by The Little Princess Trust and administered by CCLG
Funded July 2017
Award: £99,465.00
We have identified a new molecular defect in a common childhood kidney cancer (Wilms' tumour). We want to find out whether correcting this defect can stop Wilms' tumours growing and to understand the mechanisms by which this defect has its effects.
Wilms' tumour is a common childhood kidney cancer that generally has a good outcome, but importantly there are still some children who will relapse and die from their disease. Despite knowing a lot about the molecular and biological basis of Wilms' tumour, it is still difficult to predict in which children relapse will occur and difficult to cure them. This means that there is still a pressing need to find new methods for predicting which children will relapse and for treating them.
We have used modern molecular methods to examine changes that affect how genetic information (DNA) is read in childhood cancers; so-called "epigenetic" changes. Epigenetic changes do not alter the DNA code but they do prevent it being read, leading to genes being switched off inappropriately in cancer. We have found one gene that is switched off in many Wilms' tumours and some other kidney tumours by epigenetic changes, especially in advanced, aggressive tumours. This gene normally plays an important role in kidney development and it is the disruption of this normal development that underlies Wilms' tumour.
Although a number of other genes are known to be important in Wilms' tumour, this is the first time that this particular class of gene has been implicated. So we think that investigation of this gene could tell us some really novel information about how Wilms' tumour arises. Importantly, because epigenetic changes are reversible, this gene could potentially be switched back on again by drug treatment, leading to new methods for treating Wilms' tumour.
In this project we want to answer two questions:
- How does this gene work at the molecular level to influence Wilms’ tumour growth?
- If we switch the gene back on in Wilms' tumour cells, will it stop them growing in the laboratory and as tumours in an animal model?
By gaining a better understanding of how this gene influences Wilms’ tumour, we hope to be able to identify new pathways that can be targeted for treatment and also to identify molecular changes that can be used to help diagnose and predict the outcome in children with Wilms’ tumour and other childhood kidney tumours.