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About SickKids

April 7, 2014

New insight into fatal childhood brain tumour may lead to patient-targeted treatment

TORONTO – Imagine being a parent receiving news that your six-year-old child has a brain tumour that has no effective treatment, and is almost universally fatal. This is a harsh reality for the 30 children in Canada who are diagnosed each year with a rare paediatric cancer called diffuse intrinsic pontine glioma (DIPG). The failure of most therapies for this cancer can be attributed to the delicate location of the tumours and the assumption that DIPGs are similar to a type of adult brain cancer, glioblastomas.

In a new study led by The Hospital for Sick Children (SickKids), researchers have for the first time, uncovered the genetic drivers of DIPG and identified three distinct subgroups of the disease. The study demonstrates that this tumour is not only different from adult brain cancer, but the genes found have never been seen in any other cancer, including a novel cancer gene called ACVR1. The study is published in the April 6 online edition of Nature Genetics.  

Unlike other brain tumours, DIPG cannot be surgically removed because it infiltrates the wiring of the brainstem which controls vital functions such as breathing, heart regulation and movement. As a result, biopsy tissue is rarely acquired, so the genetic landscape of DIPG has not been known until now.

“This work gives us the opportunity to make some real progress for these patients and their families. We found that there are actually different genes driving the behaviour of each DIPG subgroup, which has key implications for the design of appropriate and more targeted therapy for these tumours. Put simply, it means that each subgroup will require a different therapy,” says Dr. Cynthia Hawkins, Principal Investigator of the study, Neuropathologist and Scientist in Cell Biology at SickKids.

The research team did detailed genetic characterizations of more than 60 DIPG samples, including deep-sequencing on 36 DIPGs, from across Canada, the United States, Australia and the United Kingdom, to uncover the genetic landscape of these tumours. “It was surprising how frequent the mutations were in this cancer. Most of the time when you do genetic studies you may find mutations in 5 per cent of the cases. Here we found different targetable genes in 20 to 80 per cent of the cases. This was unexpected and very encouraging because from a clinical trial perspective this could mean we have the opportunity to have a greater impact on more patients.”

Children with DIPG typically present at six or seven years old with mild neurological symptoms like weakness, limping or vision issues. Because surgery is not an option and chemotherapy has shown no benefit, radiation has been the main therapy offering short-term symptom control. Unfortunately, all children die within two years of diagnosis.

For patients with an inoperable tumour, targeted drug therapies are especially important. “With other cancers, surgeons aim to remove the majority of the tumour and follow up with radiation and/or chemotherapy to attack the remaining cancer. For DIPG, in order to make an impact the medicine would need to treat the entire tumour.”

The team says that this is still only the beginning, but the next steps are already underway as researchers are now looking specifically at each genetic mutation in each subgroup, and exploring what therapeutic targets may work.

This research would not have been possible without the patients and their families who donated tissue for this research and the support of Canadian Institutes of Health Research (CIHR), Genome Canada 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 for Healthier Children. A Better World. For more information, please visit www.sickkids.ca.

Media contact:

Caitlin McNamee-Lamb
The Hospital for Sick Children
416-813-7654, ext. 201436

Matet Nebres
The Hospital for Sick Children