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March 8, 2009

Genetic research narrows in on cause of childhood brain cancer

Researchers hope the discovery of multiple genetic mutations leads to improved cancer treatments

TORONTO – Scientists at The Hospital for Sick Children (SickKids) have discovered a family of eight genes that are mutated in patients with medulloblastoma – the most common childhood brain cancer. The research is published in the March 8 online edition of Nature Genetics.

Brain tumours, including medulloblastoma, are the leading cause of childhood cancer-related deaths. Although recent medical advances mean that up to 60 per cent of patients now survive, survivors are often left with serious physical and neurological disabilities from both the cancer and the treatments.

“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,” says senior author Dr. Michael Taylor, SickKids Neurosurgeon, SickKids Scientist, Assistant Professor in the Departments of Surgery and Laboratory Medicine and Pathobiology at the University of Toronto, and a principal investigator at the Labatt Brain Tumour Research Centre at SickKids.

In the largest study of its kind, the scientists analyzed over 200 medulloblastomas that had been surgically removed from children. They discovered that eight of the mutated genes belong to a specific family of genes that encode for proteins involved in turning genes on and off. Specifically, the genes they identified are responsible for turning off growth promoting genes as the brain grows and develops.

The way the genes normally work is that they make a protein that causes DNA to wind up very tightly. This tight winding would normally turn off the growth promoting genes once brain growth is completed. When these genes are mutated, however, growth in the developing brain does not cease and brain cancer results.

This discovery is hopeful because similar genes involved in the “winding of DNA” have already been successfully targeted by drugs. The researchers hope to develop new therapies for childhood brain cancer that will result in more survivors, and an improved quality of life for survivors.

“Cancer biology, with the help of the human genome project, is moving along rapidly. 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,” says Paul Northcott, a PhD student in the Taylor lab and first author on the study.

“Given adequate resources, we could discover all of the 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.”

The study was supported by the Canadian Cancer Society, the Pediatric Brain Tumor Foundation, Sontag Foundation Distinguished Scholar award, SickKids Foundation, The Neurosurgery Research and Education Foundation, BRAINCHILD, the 407 Express Toll Route and the Walker Family, the Laurie Berman Fund in Brain Tumor Research, the American Brain Tumor Association, Clinician-Scientist Award of the Canadian Institutes of Health Research, and a SickKids Restracomp award.

The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, is Canada’s most research-intensive hospital and the largest centre dedicated to improving children’s health in the country. As innovators in child health, SickKids improves the health of children by integrating care, research and teaching. Our mission is to provide the best in complex and specialized care by creating scientific and clinical advancements, sharing our knowledge and expertise and championing the development of an accessible, comprehensive and sustainable child health system. For more information, please visit www.sickkids.ca. SickKids is committed to healthier children for a better world.

For more information, please contact:

Matet Nebres
The Hospital for Sick Children
Phone: 416-813-6380
email: matet.nebres@sickkids.ca

Suzanne Gold
The Hospital for Sick Children
Phone: 416-813-7654 ext. 2059
email: suzanne.gold@sickkids.ca