Canadian researchers are a step closer to unraveling the mystery of the most common form of childhood brain cancer, called medulloblastoma.
Scientists at the Hospital for Sick Children have discovered a family of eight genes that are mutated in patients with medulloblastoma. The discovery is an early first step, but it could lead to better, more targeted treatments so that more of the children diagnosed with the cancer can survive.
Brain tumours are the leading cause of cancer deaths in children, and medulloblastoma is the most common. The cancer develops in very young children in the part of the brain called the cerebellum, the area that controls balance and movement.
The prognosis for children with these tumours is not great. About 40 per cent of patients will die within five years.
As well, the treatment, which includes surgery, radiation and chemotherapy, is harsh and aggressive and often damages the children's developing brains, says SickKids neurosurgeon Dr. Michael Taylor.
"Of the children who do survive, many have long-term problems with cognition, neurological problems, and the risk of other cancers down the road," says Taylor.
The cause of medulloblastoma is unknown but is thought to be triggered by random, not inherited, errors in the genes. Now, Taylor's team is a little closer to identifying those causes by isolating these eight genetic mutations -- mutations that had never before been suspected as culprits in cancer formation.
"When these eight genes are functioning normally, we believe their role is to make a protein which tells the developing brain when it's time to stop growing," explains Taylor. "But when the genes are mutated, the brain may continue to grow out of control, leading to cancer."
In the study, the largest of its kind, researchers looked at more than 200 tumour samples that had been surgically removed from children in countries around the world, including Canada, the U.S. and Saudi Arabia.
Drugs could be adapted for treatment
Paul Northcott, a PhD student in Dr Taylor's lab, analyzed and interpreted all the data over a period of three and half years.
"We've learned more from this study about the genetic basis of this disease than from any other previous study," Northcott says.
He says work in his field has been accelerated by progress in the human genome project.
"Technology to detect mutations is so powerful now that one person can do what would have required thousands of people just five to 10 years ago," he says.
"Given adequate resources, we could discover the entire important gene mutations in childhood brain cancer within the next five years, and then move on to figuring out how to target those mutations to improve cure rates and decrease complications."
Taylor says drugs are already being developed that target the type of proteins that are issing in the brains of children with the gene mutations.
"Our hope is that some of these drugs may be adapted and used effectively to treat medulloblastomas," he says.
"By developing a better understanding of the biology of the mutated genes that drive the formation of medulloblastoma, we hope to be able to design better therapies that will kill tumour cells without having a toxic effect on the developing brain," he says.
The research is published in the online edition of Nature Genetics.
With a report from CTV's medical specialist Avis Favaro and producer Elizabeth St. Philip
