Treatment for childhood cancers could change after a genetic study of childhood cancers co-led by Cambridge researchers revealed that they contain many more genetic changes than previously thought, and found a gene responsible for causing some childhood kidney cancers.
Until now, scientists have believed that the genetics of children’s cancers are simpler than those in adults, with fewer changes between healthy cells and cancer cells.
This view has been overturned by a study published today (29 May) in Nature Communications, which used some of the latest genetic sequencing technology to show that tumours in children could contain millions of genetic changes.
The study used samples collected from young children with Wilms tumour – a kidney cancer that largely affects children under the age of five. In the UK, about 85 children are diagnosed with Wilms tumour every year.
It has been a widely held belief that childhood tumours had much lower numbers of genetic changes than adult tumours. However, thanks to the development of new genomic sequencing tools, we have been able to show that, at least in these cases, it is not true.
Professor Sam Behjati, study co-senior author, Cambridge University Hospitals NHS Foundation Trust (CUH) and Wellcome Sanger Institute.
This discovery could lead to new treatments and may mean that treatments currently only used for adult cancers, such as immunotherapies, could also deliver benefits for some children.
The study used innovative sequencing tools to analyse the genetics of cancers in much greater detail. Previous studies used ‘mass sequencing’ that looks at the average genome across hundreds of cells. In this study, the team were able to look at genomes from individual cells, which allowed the scientists to find many more genetic changes.
With these latest genomic sequencing techniques, we can now see a much more detailed picture of Wilms tumour, which can occur in newborns. This could help us understand this condition in more detail, and may change the way we view and treat childhood tumours as a whole.
Dr Henry Lee-Six, co-first author at the Wellcome Sanger Institute
The study focused on samples collected from four children under six months old that had Wilms tumour. Analysis of the samples found hundreds more genetic changes in each cell than expected.
Our findings suggest that childhood tumours have at least four times more genetic changes per cell than expected, which adds millions more changes per tumour, highlighting that what we could see before was just the tip of the iceberg. This has implications for both childhood kidney cancer and possibly other childhood tumours.
Professor Sam Behjati, study co-senior author, CUH and Wellcome Sanger Institute.
The authors of the study suggest that this could change the way children’s cancers are treated. A high number of genetic changes may help children’s cancers to resist some treatments, but it may also make them susceptible to other treatments that have previously only been used in adults.
Further analysis of the results revealed that a single genetic change in a gene called FOXR2 may cause a certain rare form of Wilms tumour. The change affects kidney development before birth, leading to tumours developing.
This form of Wilms tumour is easy to identify under a microscope, and this discovery could allow precision medicines to be developed to specifically target these tumours.
In this study, we uncovered a single genetic change that occurred during development and caused this subset of Wilms tumour. … By understanding the genetic changes that cause tumours, and in this case, identifying different genetic subsets, it could lead to more targeted treatment options, something that every child deserves.
Dr Jarno Drost, co-senior author at the Princess Máxima Center for Pediatric Oncology and Oncode Institute, the Netherlands
The work has been co-led by Professor Sam Behjati, honorary consultant paediatric oncologist at CUH, clinical professor of paediatric oncology at the University of Cambridge and a group leader at the Wellcome Sanger Institute.
Improving insights into the origins of childhood cancers, and using genomics to improve treatment are key goals of the new Childhood Cancer Centre within the Cambridge Children’s Hospital Research Institute. Professor Behjati will lead the Centre, which will also seek to improve survival and reduce the lifelong impacts of childhood cancer treatments. Cambridge Children’s Hospital will be built on the Cambridge Biomedical Campus, with construction due to begin in 2026.
The research involved an international team including those at the Wellcome Sanger Institute, Addenbrooke’s Hospital, University of Cambridge, Princess Máxima Center for Pediatric Oncology and Oncode Institute in the Netherlands, and Great Ormond Street Hospital.
Learn more about this story from the Wellcome Sanger Institute.
