In a project supported by Genome BC, a Vancouver pediatric pathologist at the BC Cancer Agency/University of British Columbia is leading the team that will explore the genomes (DNA) of four of the most challenging childhood cancers known. Dr. Poul Sorensen and his colleagues in the Canadian Pediatric Cancer Genome Consortium hope to find the link between primary and metastatic tumours using revolutionary genomics technology and a highly skilled consortium of scientists and clinicians.
Most cancer deaths are not caused by the primary disease; rather, it is the invasion and spreading of mutated cells to distant sites in the body (metastasized tumours) that tend to give a poor prognosis for the patient. Using next generation sequencing to rapidly scan the DNA of primary tumours, metastatic tumours and normal tissue, Sorensen and his team are discovering fundamental differences between primary and metastatic disease tissue. This knowledge will not only help to determine how to better treat childhood cancers but more importantly give insight into how to prevent tumours from metastasizing to other parts of the body. If the team can determine which genetic mutations cause the disease to spread, then appropriate therapies can hopefully be designed and/or re-directed to prevent metastasis.
"There is little known about metastatic disease in either pediatric or adult cancer," says Sorensen. "Our biggest challenge to improving survival is to understand the biology of metastatic disease and how to target it." If the team can determine all possible genetic mutations and study a cohort of samples, they can identify the common mutations and determine which mutation is in fact driving the spread of disease. The motivation for the project stems from a lack of understanding in the background mutation of tumours from primary to metastatic progression. "It is imperative to understand metastases and this is an area that has not been well researched on a genomic level internationally," Sorensen adds.
The team will focus on medulloblastoma (brain cancer), metastatic osteosarcoma (bone cancer) and two other types of pediatric brain tumours to uncover genetic abnormalities that direct tumour cells to spread or become resistant to treatment. They will examine and directly compare the genetic signature of each of these diseases in primary tumour cells and tumour cells that have metastasized or relapsed. These studies will produce a first-time view of the tumour genomes in these diseases. This insight not only provides immediate potential for improving tailored therapies for children with these lethal cancers, but will enable the future development of new drugs for patients who otherwise have limited options for treatment.
"Genome BC is thrilled to be funding this essential and ground-breaking work. Our hope is that the results from this research will impact not only on childhood cancers but to shed light on the link between primary and metastatic tumours for all cancer patients," says Dr. Alan Winter, President and CEO of Genome BC.
"Having the genetic, biological and clinical expertise in Vancouver makes this an ideal place to lead this research. The research team has access to rare samples and can tap into an international network to allow for a quick and easy liaison from bench to bedside," says Sorensen. The mutational landscape of cancer cells is nearly impossible to find with only one tumour to analyze; however, with a national network and international linkages the team can begin to make the imperative connections between normal and mutated genes across a larger group of cases.
The $2.8 million (CDN) research project is also funded by the Canadian Institutes of Health Research (CIHR), Genome Canada, Genome Quebec and the C17 Research Network.