Understanding the order of genetic changes that lead to Wilms tumour to improve treatment

Wilms’ tumour is a common childhood cancer of the kidney, mainly affecting toddlers. Although many children suffering from Wilms’ tumour can be cured, the treatment is often harmful in the short and the long term. In addition, some children cannot be cured, despite most aggressive treatment.

Wilms’ tumour, like all other human cancers, is caused by changes (mutations) in the DNA, the genetic code of cells. Although we have a reasonable understanding of what the mutations driving Wilms’ tumour are, we do not know in which order these arise. If we knew the order, we might be able to identify the most critical mutations that cause Wilms’ tumour. We could then prioritise these critical mutations in efforts to find novel drug targets in Wilms’ tumour.

The aim of our experiment therefore is to define the order in which mutations arise that underpin Wilms’ tumour.

Technological and analytical advances in our ability to read DNA sequences have made it feasible to read the entire genetic code of human cancers (whole genome sequencing). In this experiment we are proposing to apply whole genome sequencing, along with other sequencing techniques, to Wilms’ tumour. What is unique about this experiment is that we have designed it in a way that allows us to find out the order in which mutations have occurred. We are focusing on bilateral tumours from three children. The tumours for this experiment have been collected under the IMPORT study.

The key outcome of our experiment will be a precise developmental map for each pair of tumours, with an exact time sequence of mutations. This study is likely to provide an unprecedented insight deep into the origins of Wilms’ tumour. Here we may identify key mutations that represent the Achilles’ heel of Wilms’ tumour.