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Cancer is the most common cause of non-accidental death in children from infancy to young adulthood. In Canada, ~1,400 children (0-18 years of age) will be diagnosed with cancer every year. Approximately 200 will die and many more will live with life-long complications of their disease and treatments. Expert clinicians in childhood cancer and research scientists have probed the genomes (DNA) of six of the most challenging childhood cancers known. The project team used leading edge ”next generation sequencing” technology to rapidly scan the DNA of the entire genome that is contained in tumor cells and examined and directly compared the genetic signature of primary tumour cells and tumor cells that have spread (metastasized) or relapsed in childhood medulloblastoma (brain cancer), metastatic osteosarcoma (bone cancer) and recurrent leukemia (cancer of white blood cells), to uncover genetic abnormalities that direct tumor cells to spread or become resistant to treatment. In addition, they determined the gene signatures of three highly lethal childhood brain tumours to uncover new genes that may be targets for new drug therapies.

Through this project, researchers have been able to advance their understanding of the genetic underpinnings of these diseases, file a patent on a novel cancer gene for Diffuse Intrinsic Pontine Glioma (DIPG), and initiate development of a diagnostic test for DIPG histone mutations, for use in the clinical CLIA approved laboratory at the Hospital for Sick Children, Toronto. In addition, this project has led to one of the largest integrated molecular and clinico-pathologic analyses of ATRTs that involved 35 institutions globally. Through this effort, this group has been able to produce a first molecular framework for treatment stratification of children diagnosed with ATRTs. Data derived from NGS will be validated in independent cohorts of clinically annotated patient samples available through the international collaborative networks of the PIs (such as the C17 network of all pediatric oncology centers in Canada and the Children’s Oncology Group (COG). This project also provided the opportunity to study the many ethical issues that arise in deciding when and how best to provide the results from genetic studies on childhood cancers back to the patients and their families. Long-term potential – improving tailored therapies for children with these lethal cancers (improved survival and reduced long-term consequences for children with cancer), and leading to improved clinical trials to enable the development of new drugs for patients who otherwise have limited options for treatment.