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January 6, 2010

SickKids researchers find powerful predictor of bone cancer prognosis

TORONTO – Scientists at The Hospital for Sick Children (SickKids) have discovered a powerful new tool that can help predict the prognosis for patients with bone cancer and help doctors more accurately determine how aggressively they need to treat specific patients. They found that the presence of a specific type of genetic mutation found in the tumours results in poorer outcomes for patients with osteosarcoma – the most common bone cancer in children and adolescents. The study is published in the current issue of Cancer Research.

The research team analyzed tumour DNA from osteosarcoma patients and found a novel region called osteo3q13.31, which contains three genes that were previously not known to be involved in the disease. They used the presence or absence of a mutation in these genes – known as an osteo3q13.31 deletion – as an indicator to predict the disease outcome in osteosarcoma. They studied 49 patients and found that a deletion resulted in poorer outcomes.

“This marker is an incredibly powerful tool. If the deletion is present, this suggests that the patient would need more aggressive therapy than if it is absent,” says principal investigator Dr. David Malkin, Paediatric Oncologist and Senior Scientist at SickKids, and Professor in the Department of Paediatrics at the University of Toronto. “Hopefully, we would be able to avoid over treating patients who don’t need the most aggressive therapy, while ensuring that we aren’t under treating those who do.”

The advent of high-resolution technologies allowed the scientists to look at regions of DNA with much more clarity. The scientists used a high-resolution tool called single-nucleotide polymorphism (SNP) array to look at copy number alteration (CNA).  CNA is a genetic phenomenon that occurs when some regions of the DNA are duplicated or deleted. Normally genes are present in two copies, with one copy inherited from each parent. CNAs are often found in osteosarcoma.

Every year, there are about 300 new cases of osteosarcoma in Canada, most of which occur in adolescents and young adults. The survival rate of about 65 per cent has not changed in about two decades. While the first step is to use the new marker as a prognostic tool, Malkin says it may eventually be used as a therapeutic target, ultimately leading to improved survival rates for osteosarcoma. Down the road, the marker may also be able to help determine prognosis in tissue cancers including carcinomas and sarcomas, he explains.

     
The image on the left shows two copies of osteo3q13.31 (green) in a tumour cell. 
The image on the right shows a full osteo3q13.31 deletion.

The research was supported by the Canadian Institutes of Health Research and SickKids Foundation.

About The Hospital for Sick Children
The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally.  Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system.  SickKids is proud of its vision of Healthier Children. A Better World.™ For more information, please visit www.sickkids.ca. 

About Peter Gilgan Centre for Research and Learning 
The Peter Gilgan Centre for Research and Learning will bring together researchers from different scientific disciplines and a variety of clinical perspectives, to accelerate discoveries, new knowledge and their application to child health — a different concept from traditional research building designs. The facility will physically connect SickKids science, discovery and learning activities to its clinical operations. Designed by award-winning architects Diamond Schmitt Architects Inc. and HDR Inc. with a goal to achieve LEED® Gold Certification for sustainable design, the Gilgan Centre will create an architectural landmark as the eastern gateway to Toronto’s Discovery District. The Peter Gilgan Centre for Research and Learning is funded by a grant from the Canada Foundation for Innovation, the Government of Ontario, philanthropist Peter Gilgan and community support for the ongoing fundraising campaign. For more information, please visit www.sickkidsfoundation.com/bepartofit.

For more information, please contact:

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