Genetic breakthrough in childhood kidney cancer

Scientists from the Princess Máxima Center, working with partners from the Wellcome Sanger Institute, the University of Cambridge and Great Ormond Street Hospital in the UK, have used new DNA technologies to examine tumors from young children with a kidney tumor in detail. They used advanced sequencing, a method that allows scientists to quickly and extensively read out the entire genetic material of the tumor.

More variation than expected

By genetically mapping individual cells of Wilms tumors, the researchers found many more mutations per cell than expected. Dr. Jarno Drost, research group leader at the Princess Máxima Center and Oncode Institute, is co-senior author of the new study. He says: ‘Our findings show that the genetic variation of some childhood tumors is much higher than previously thought. In some cases, it’s even comparable to that of tumors in adults.’ The findings change the assumptions we had of childhood cancer and also point to opportunities for new or existing therapies.

Implications for treatment

Tumors with a lot of genetic variation can adapt more quickly, so a treatment can stop working. But large variation in the tumor also offers targets for precision therapies such as immunotherapy. These treatments, now mainly used in adult oncology, could in future also be used in children with Wilms tumor.

Unique genetic change in congenital tumors

Another important discovery in the research is a specific genetic change (in the FOXR2 gene) that already occurs during embryonic development. This mutation appears to be responsible for a rare congenital form of Wilms tumor, with specific features under the microscope, and with a characteristic genetic profile. Spotting this mutation could in future help to personalize treatment for children with a Wilms tumor.

Careful balance

Jarno Drost: ‘The treatment of Wilms tumors requires a careful balance: targeting the tumor and preventing the cancer from coming back, with as little impact as possible on the quality of life of a child and their family. We now better understand which genetic changes cause these tumors, and can better pick out these genetic subgroups. Our research marks an important step towards more targeted and child-friendly treatments.’

This study was published today in Nature Communications. The research was led by Dr. Sam Behjati of the Wellcome Sanger Institute in the UK and Dr. Jarno Drost of the Princess Máxima Center and Oncode Institute. The research was funded by the Alpe d’HuZes/KWF fund, ERC, the Wellcome Trust and the Little Princess Trust.