Principal Investigator: Dr Sorana Morrissy
University of Calgary, CanadaTags: 43898, cancer, inherited, pediatric, predisposition
Cancer is the leading cause of disease-related death in children. Despite recent increases in cure rates for childhood cancers to ~80%, more than two thirds of children treated with surgery, chemotherapy, and radiotherapy suffer long-term side effects including learning disabilities, organ toxicities, and recurrent cancer that is nearly always incurable. Since DNA is the genetic blueprint that ultimately dictates the proper functions of cells in our bodies, we need to improve discovery of the genetic changes that lead to cancer in order to design safer and more effective therapies. Research efforts have largely focused on those genetic events that are acquired during the lifetime of the patient and which can change normal cells to cancer cells. However, we know that some of the genetic changes predisposing children to cancer can be inherited from parents: it is these important inherited changes that are less well studied and understood. We propose to identify and study inherited changes in the DNA of childhood cancer patients, and find those unlucky combinations that play a role in cancer initiation. Long-term barriers to this work have revolved around the enormous amount of events that must be considered, and the insufficient number of normal samples with DNA information that could be used as a control dataset. The vast collection of normal individuals with data collected by the UKBioBank now makes a detailed and complex search for inherited “smoking guns” possible. Over the next 1-2 years, we will use various statistical and machine-learning approaches to systematically explore the genetic differences between kids with cancer and normal adult individuals, paving the way for a better understanding of how early-life cancers start, and ultimately for development of new therapies.