A Luminesce Alliance-funded trial looking at the genomic sequencing of patients diagnosed with childhood cancers is providing vital insights into whether some children are predisposed to develop the disease.

When children and adolescents present to hospitals with cancer, we often suspect it may be caused by changes in their DNA that damage the genes they were born with. But we do not know why some children get cancer, how many of them have an underlying genetic abnormality that predisposes them to cancer, or what this means for the future management of these children and their families.

Our pilot program allows all children diagnosed with cancer in New South Wales access to family-based DNA testing. The PREDICT study will help give the world a much clearer picture of how changes in genes we are born with contribute to the risk of developing childhood cancer and help us find ways of managing it.

We have already recruited more than 100 families to the study.

Our findings will show whether routine family-based germline testing of children with cancer is feasible and beneficial, what percentage of children with cancer have a genetic predisposition, and what the implications are for them and their families and how they are managed.

About 8 per cent of childhood cancers may have a genetic cause. But whole genome sequencing of children with high-risk, aggressive cancers who were enrolled in the Zero Childhood Cancer Program (ZERO) over the past five years, found that double that number as many as 16 per cent had reportable genetic variants thought to be responsible for their cancer.

To understand the full spectrum of these genes and variants and the contribution of heritable germline variants in the development of all paediatric cancer, it is necessary to broaden genomic germline sequencing to all children with cancer.

Luminesce Alliance funding has been used to develop and launch the PREDICT trial, which involves whole genome sequencing of the germline of every child diagnosed with cancer in NSW.

Understanding the genetic predisposition to cancer will have several benefits for the child and their extended family, says Dr Luciano Dalla- Pozza, Director of the Cancer Centre for Children at The Children’s Hospital at Westmead.

For example, it will influence treatment recommendations and play a role in determining outcomes, such as whether a child may respond well to radiotherapy or certain medications.

It provides the opportunity of personalising surveillance programs and implementing early intervention and lifestyle changes to prevent or treat cancer at an earlier stage.

“It also provides valuable information to patients and their families to help them make choices about future pregnancies, to understand how to minimise their own cancer risk and that of any future children they may have,” says Dr Dalla-Pozza.

Ultimately, if the PREDICT trial indicates that this work is feasible and useful, it will inform the roll-out of a national cancer predisposition pilot screening program through the Zero Childhood Cancer Program’s clinical network.

In the long term, that program will provide the opportunity to personalise surveillance and treatment plans for children and their families who are found to be at risk of cancer due to heritable germline variants.