Gene discovery raises new treatment guide hope for aggressive childhood cancer

Scientists have identified key genetic changes associated with the development of an aggressive form of childhood cancer that could lead to improved decision making in assigning treatments.

A team of international researchers have discovered mutations in certain genes that are linked to worse survival outcomes for rhabdomyosarcoma, a rare type of cancer that forms in soft tissue that affects children.

They said the findings, published in the Journal of Clinical Oncology, will improve the current system for assessing a child’s risk and guide treatment of individual patients.

It means some children could be more intensively treated, while others could be spared aggressive interventions.

Study leader Janet Shipley, Professor of Molecular Pathology at The Institute of Cancer Research, London, said: “Our findings shed light on the genetic changes that underlie rhabdomyosarcoma, a rare and aggressive childhood cancer.

“By looking at the genetic features of different tumours, we can divide children into different risk groups to help guide their treatment.

“Decades of clinical trials have led to the current complicated system for assigning risk to children with rhabdomyosarcoma – but we know that the current system is not accurate enough to properly assign treatment for individual children.

“Our findings should refine the current system and treatments clinicians provide to more effectively match each child’s genetic profile and risk.

“Ultimately, further research may highlight new drugs to tailor treatment for patients with high-risk rhabdomyosarcomas that have specific genetic defects.”

The study, funded by Cancer Research UK and other charities such as Chris Lucas Trust, Talan’s Trust and Alice’s Arc, analysed DNA from 641 patients with rhabdomyosarcoma.

The scientists found that mutations in the genes known as MYOD1 and TP53 were associated with significantly poorer response to treatment and worse survival outcomes for children with fusion-negative rhabdomyosarcoma – a sub-type of the disease.

They also believe that having too many copies of another pair of genes – called CDK4 and MYCN – may also be linked to a poorer outcome in another subtype of rhabdomyosarcoma that is fusion-positive.

Fusion gene-positive or fusion gene-negative rhabdomyosarcoma, depends on the presence of a “fusion gene”, which is a hybrid gene formed from two previously separate genes.

The team believes using targeted drugs such as tipifarnib, may be particularly beneficial for high-risk patients.