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About SickKids

December 8, 2009

SickKids-led international study identifies important piece of puzzling brain tumour

An international team of scientists have made an important breakthrough in describing a rare type of brain tumour that currently delivers a grim prognosis to the young children stricken by it.

The study, led by researchers at The Hospital for Sick Children (SickKids) and reported in the December 8 edition of Cancer Cell, is a collaboration with centres in the United States, United Kingdom, Italy, Taiwan and China. Scientists call it a step closer to earlier diagnosis and better therapies for children afflicted with Central Nervous System-Primitive Neuroectodermal Tumours (CNS-PNET).

The research team discovered a large cluster of microRNA (miRNA) genes, called C19MC, which were amplified in aggressive CNS-PNET cells. The cluster functions as a group of oncogenes, which are genes that cause normal cells to transform into cancerous ones. MiRNAs are a newly-discovered class of tiny RNA molecules that typically regulate gene expression; when amplified, these miRNAs are capable of stimulating the growth of cancerous tumours.

“Normal neural stem cells don’t keep multiplying,” says Dr. Annie Huang, principal investigator of the study, who is also a Staff Oncologist in the Paediatric Brain Tumour Program, Scientist, and Principal Investigator at the Arthur and Sonia Labatt Brain Tumour Research Centre at SickKids. “Here, they have somehow lost the stop signal and keep growing.”

Until now, scientists have had limited opportunities to study CNS-PNETs because they are uncommon, representing only three to seven per cent of all paediatric brain tumours. Through this international collaboration, the research team was able to collect over 100 tumours and analyze about half of them.

CNS-PNETs are difficult to diagnose, as they resemble other types of brain tumours, most notably medulloblastomas, which are the most common childhood brain cancers. Diagnoses of CNS-PNET brain tumours are generally made by exclusion, meaning if the tumour does not fit into other categories, it may be classified as CNS-PNET. As a result, these tumours are often misdiagnosed as other types of tumours. If the tumours are correctly diagnosed, it is often at an advanced stage, and current treatments are not very effective.

“Until now, we thought this was one of the more uncommon groups of paediatric brain tumours; maybe it’s not as uncommon as we think,” says Dr. Annie Huang, an Assistant Professor in the Department of Paediatrics at the University of Toronto. “One of the major challenges with paediatric brain tumours is that a lot of them look the same. This particular type of tumour looks like medulloblastoma in the pathology; the only way to tell that it is CNS-PNET is by the location.”

Signs and symptoms of CNS-PNETs are often nonspecific and range from nausea and vomiting to headaches, seizures, a large head, to losing developmental milestones, among others. The tumours appear at the top of the head – the “thinking” part of the brain – so radiation is a limited treatment option. The tumours are typically treated with high-dose chemotherapy, three bone marrow transplants and surgery. The tumours appear most often in young children up to preschool age and the survival rate is less than 20 per cent.

The initial phase of the research examined the tumours through genotyping and gene-expression studies. By chance, the scientists found a frequent amplification of C19MC. “This wasn’t what we expected to find,” says Huang. “We thought it would take a little more time to find a marker. Now that we have found it, we can say that if you have this marker, the chances are you will have a recurrence.” The next step, she explains, is to study whether C19MC can be used as a diagnostic marker and to develop targeted therapies.

The prevalence of this type of tumour may actually increase over time, she says, because the marker will help confirm the diagnosis.

This study was supported by the Children’s Brain Tumor Foundation, the Canadian Cancer Society Research Institute and SickKids Foundation.