The dirty dozen: 12 new subtypes of medulloblastoma discovered

SickKids study takes another step closer to personalized medicine for kids with a form of brain cancer

By Jessamine Luck, Media Relations Intern

Medulloblastoma, the most common type of malignant brain tumour in children, was once thought to be one singular disease. In 2010, scientists at The Hospital for Sick Children (SickKids) in Toronto discovered that it was actually composed of four different subgroups, each with its own molecular composition and clinical characteristics.

Now, researchers from SickKids and around the world have found these four subgroups separate further into a dozen different subtypes the researchers are calling “the dirty dozen”. These subtypes exhibit different clinical behaviour, marking a significant step forward towards developing personalized treatment for children with medulloblastoma. The study will be published in the June 12 edition of Cancer Cell.

“Some oncologists think that heterogeneity is limited to adult cancers, but our study shows when you analyze enough samples medulloblastoma is actually composed of many different cancers that look the same under the microscope,” says Dr. Vijay Ramaswamy, Co-corresponding author, Neuro-oncologist and Scientist in the Arthur and Sonia Labatt Brain Tumour Research Centre at SickKids.

The study analyzed 763 frozen medulloblastoma samples from around the world collected through the Medulloblastoma Advanced Genomics International Consortium (MAGIC) housed at SickKids. The researchers used a novel computational method for genomic data developed at SickKids by Dr. Anna Goldenberg to identify biologically distinct subtypes of medulloblastomas. This is the largest collection of medulloblastomas to be analyzed in this comprehensive way.

“It is through interdisciplinary collaborations like these and integration of diverse types of data that we can make substantial progress in understanding complex human diseases and help to improve treatment and quality of life for our patients,” says Goldenberg, Co-corresponding author, Scientist in genetics and genome biology and assistant professor in computer science at the University of Toronto.

Currently, treatment for medulloblastoma is particularly aggressive. Once diagnosed, patients typically undergo brain surgery to remove all or part of the tumour which is followed by radiation to the brain and spinal cord and/or high dose non-specific toxic chemotherapy. Despite this aggressive treatment, the survival rate for medulloblastoma is only 60 per cent and the patients who do survive are at high risk for secondary tumours, growth delays and significant intellectual impairment.

One of the new subtypes the researchers identified was low-risk, meaning patients with this subtype could be eligible for less aggressive treatment in future clinical trials. “Our study is a first step in trying to tailor our therapies to be more personalized, which will both reduce long-term side effects of our current therapy, while increasing survival by hitting the right target,” says Ramaswamy who is also an assistant professor in paediatrics at the University of Toronto.

The study was co-led by Drs. Michael Taylor, Ramaswamy and Goldenberg and involved an international team of 95 researchers including first authors Dr. Florence Cavalli from SickKids and Dr. Marc Remke from the University of Düsseldorf.

Funders for the study included the Pediatric Brain Tumor Foundation, the Garron Family Cancer Centre, the Stand Up to Cancer - St. Baldrick’s Pediatric Cancer Dream Team Translational Grant, the Terry Fox Research Institute and the Canadian Institutes of Health Research.