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About SickKids

April 18, 2006

Researchers determine that the prognosis for some paediatric brain tumours is correlated with expression of the protein telomerase

A team of researchers from SickKids has identified a new prognostic marker for two types of paediatric brain tumours related to the expression of the protein telomerase. This research was reported in the February issue of the journal Neoplasia and the April issue of the Journal of Clinical Oncology.

Each time a normal cell divides, its chromosomes, which contain the cell’s genetic material, divide as well and their ends, known as telomeres, will shorten slightly. After many generations of cell divisions, the chromosomes eventually shorten to a point that is not compatible with cell survival, and division no longer occurs. Cancer is a disease in which cells continuously divide and overcome death signals. One explanation for this behaviour is that cancer cells, unlike normal cells, contain a protein called telomerase. In the presence of telomerase, shortening of the chromosome does not occur, and continual cell division is maintained.

In the Neoplasia paper, the group investigated the telomere length in low-grade gliomas, a common type of childhood brain tumour. Low-grade gliomas are generally slow growing, non-invasive, non-metastatic tumours that carry a much better prognosis than their fast-growing, highly invasive, potentially metastatic, high-grade glioma counterparts.

High-grade gliomas almost always grow back even after complete surgical excision, radiation therapy and chemotherapy. Conversely, low-grade gliomas can often be observed for years without requiring treatment.

“We discovered that the reason the low-grade gliomas are low-grade is because they lack the telomerase enzyme and that their telomeres shorten over time, thus limiting their growth potential,” says Dr. David Malkin, the study’s principal investigator, staff oncologist, senior scientist in Cancer Research, and associate chief of research (Clinical). “This observation provides the opportunity for clinicians to use this prognostic marker to eventually to predict how long the tumour may continue to grow. This information could help tailor treatment decisions for patients based on the levels of telomerase expression in their tumours.”

In the Journal of Clinical Oncology paper, the research team studied highly aggressive brain tumours called ependymomas. People of all ages, including children, can develop ependymomas. Using a tissue microarray system, the team measured the telomerase expression in a large number of ependymomas and discovered that tumours with low expression of telomerase had a better outcome than those expressing high amounts of telomerase.

“Up until now, there have been no good prognostic markers for ependymomas,” says Dr. Cynthia Hawkins, the study’s principal investigator, staff pathologist and scientist-track investigator in Cancer Research. “Many studies are demonstrating the lifelong challenges faced by children who have undergone chemotherapy and radiation. Identification of new biological prognostic markers may help us to predict when use of those treatment options is most appropriate. Further, the finding that telomerase is so important in the aggressive behaviour of some ependymomas makes it an exciting potential target for new treatment development.”

“Our next step is to design new treatment strategies and tailor these treatments to the patient, based on their tumour’s telomerase expression levels,” says Dr. Uri Tabori, study lead author and clinical research fellow at SickKids. “We are also investigating potential ways to interfere with telomerase function in these tumours, and the behaviour of telomerase in normal, non-cancerous cells so we can better understand the function of this protein.”

Other members of the research team were Dr. Maria Zielenska, Dr. James Rutka, Dr. Eric Bouffet, Ute Bartels and Jing Ma from SickKids and Dr. Jeremy Squire, Ilan Braude and Bisera Vukovic from the Ontario Cancer Institute.

This research was supported by B.r.a.i.n.child Canada, the Canadian Friends of Tel-Aviv University/Hospital for Sick Children Medical Exchange Program, the Jonathon Hill Memorial Fund, SickKids Foundation, the Canadian Institutes of Health Research/Eli Lilly and Cancer Care Ontario through a scientist award to Hawkins.

SickKids Foundation is the largest non-governmental granting agency in child health in Canada. Established in 1972, the Foundation has granted over $500 million to The Hospital for Sick Children and over $65 million to researchers across the country. The mission of the Foundation is to inspire our communities to invest in health and scientific advances to improve the lives of children and their families across Canada and around the world.

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