Project Leaders:   
Michael Taylor, David Malkin, Marco Marra

Involved Institutions:   
Hospital for Sick Children (Toronto), Genome Sciences Centre

Technology Applications:   
Childhood cancer genomics; personalized medicine

Research Funding Program:   
Genome Canada 2010 Large-Scale Applied Research Project Competition

Cancer is the leading cause of non-accidental death in Canadian children, and brain tumors (medulloblastoma) are the leading cause of pediatric cancer deaths. Those children who do manage to survive usually have a severely impaired quality of life due to the aggressive treatment for the disease. This results in a staggering burden of suffering for children and families in Canada, as well as an economic burden estimated at over $100 million annually on the Canadian health care system. Strategies are needed to improve the quality of life for Canadian families of children with brain tumors, to increase survival rates, and to minimize the impact on health care systems.

Pilot data from our group suggests that some children with very good prognosis medulloblastoma are being over-treated with current regimens and could be spared complications by reducing the amount or type of treatment they receive. On the other hand, children with very poor prognosis medulloblastoma all die despite going through painful therapies that may in fact be futile. Reducing therapy in this group of patients could increase quality of life without changing their prognosis.

Here, we will study 1000 medulloblastomas gathered from around the world. We will scan the entire genome (DNA) of the cancer cells to discover subgroups of medulloblastoma that are genetically similar or even identical, and develop specific markers that can then be used to more accurately classify them for treatment in clinical trials. We will also identify genetic changes in the paired blood samples of these patients that may identify risk factors that predispose children to this type of cancer. We will identify subgroups of children with medulloblastoma who have poor quality of life, and prioritize them for study. We will work with families to quantify what additional risks they are willing to assume in reducing therapy to improve quality of life.

As the proposed experiments unravel the genetic basis of this most devastating of childhood cancers, we will concurrently engage global childhood clinical trials consortia to initiate trials of therapy - sparing treatment of medulloblastoma within the time frame of the project period. We anticipate that these studies will transform the way that children with medulloblastoma are treated and will have an immediate and lasting positive impact on both the survival and quality of life of children with this disease.