Novel Genetic Test Predicts Aggressive Forms of Childhood Cancer

Rhabdomyosarcoma is the most common soft tissue sarcoma in children.

New research suggests that a novel genetic test can identify which patients will suffer more aggressive forms of the childhood cancer rhabdomyosarcoma.

The study was able to positively identify high-risk children who might benefit from more intensive treatment by examining the activity of 5 genes in a tumor sample. The findings could lead to personalized treatments for children with cancer based on the genetic activity of their tumors.

The 5-gene signature, known as MG5, was developed by researchers at The Institute of Cancer Research (ICR) in London. The test was validated in samples from 68 patients led by scientists from the Children’s Oncology Group in the United States, in collaboration with the ICR.

The test for gene expression is the first of its kind to accurately predict which children with a type of rhabdomyosarcoma called fusion-negative will have more aggressive forms of the disease.

These fusion-negative tumors are deficient in particular genetic defects often found in rhabdomyosarcoma that results in 2 genes, PAX3 and FOXO1, becoming fused together.

Rhabdomyosarcoma is the most common soft tissue sarcoma in children and strongly resembles muscle tissue. The severity of the condition depends on numerous factors, including where in the body it originally developed.

“Our research showed a significant link between a particular gene signature from tumor samples and higher-risk, aggressive rhabdomyosarcoma,” said UK study lead Professor Janet Shipley, professor of Cancer Molecular Pathology at ICR. “This study is an important step towards introducing an approach that identifies children who are unlikely to benefit from current, standard treatments and can be offered more intensive or new treatment strategies that will improve their outcome.

"We now hope to bring our test for this gene signature to the clinic as soon as possible. Our aim is to identify these high-risk cases of rhabdomyosarcoma more quickly in the clinic, and ultimately improve treatment for these children.”

Previous studies have shown that fusion-negative patients have a lower risk profile for developing aggressive disease than fusion-positive cases.

The new study showed something different, however, that the ICR’s MG5 test splits fusion-negative patients into 2 groups.

Those patients with higher scores have significantly worse rates of survival than those with lower scores, indicating that the test could ultimately be included in an assessment of children with rhabdomyosarcoma across Europe and the United States to determine the best treatment option.

“We’re determined to bring the same kind of molecular advances that are starting to transform treatment for adult cancer patients to children too,” said Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London. “A key step is to begin dividing up children’s cancers depending on their genetics and gene activity, so that we can adjust their treatment according to the aggressiveness of the disease. That should help us to increase the chances of survival in those with aggressive cancer, while easing the side-effects from treatment in less deadly forms.”