Wilms Tumour is the most common kidney cancer of childhood. Most patients are treated successfully, but in a minority of cases the tumour recurs and the children respond poorly to current therapies.
We are especially interested in what makes these relapsing tumours different to other cases. We have found that the genome (DNA) in these tumours tends to be damaged in particular ways – in some cases there are extra or missing copies of certain regions of the genome, and in others specific genes are mutated.
In a small number of cases, we have access to samples both from the original tumour and from later relapses (distant metastases or local recurrences), so they can be compared directly. To learn everything we can from these cases, we need to use techniques that give us as much information as possible about any genetic changes that may have occurred in each specimen. Using ‘whole exome sequencing’ (£600 per sample) and ‘copy number microarrays’ (£150 per sample) we can scan all 20,000 genes in the genome for mutations and extra or missing copies.
With your funding, we have for the first time been able to look in depth at two recent cases with tumour recurrence, the second of which had multiple relapses. In this case, every specimen we analysed had a different set of mutations unique to that sample, showing us how the cancer changed over time, but three genes were commonly mutated in every sample – probably the key ‘driver’ genes that first made the cells cancerous.
Analyses like this have the potential to help the individual patients by identifying damaged genes suitable for ‘targeted’ therapies (personalised medicine). They also give us important insights into the development of Wilms Tumour in general, highlighting genes that may inform the design of novel clinical tests or therapeutic agents.
The UCL Research Team
We’re very grateful to Treating Children with Cancer for generously supporting our work on Wilms Tumour, the commonest childhood kidney cancer. With this funding, we have for the first time been able to apply ‘personalised genomics’ to samples from individual patients, looking for mutated (damaged) genes that might be targets for new drug treatments. A minority of children with Wilms Tumour don’t respond well to standard therapies, and we hope that this new approach will help us find more effective ways of treating them.
– Kathy Pritchard Jones