Project Overview

Need for project: Replication repair deficiency (RRD) is a genetic condition that significantly increases the risk of developing cancer, particularly early in life. Gliomas are the most common brain tumour seen in children and young adults (CAYA), and occur frequently in RRD. Currently, the prevalence of RRD has not been well described in CAYA patients. New treatments are currently available, which are more effective for this population than standard therapy. New tools are needed to recognize this condition.

Goal of project: We aim to describe the proportion of tumours with RRD in gliomas from CAYA. Currently, testing is done for this when there is a family history consistent with this condition. It is likely that the true frequency is higher and these patients are under-identified. Using more accurate testing, identifying unique characteristics through imaging and testing novel vaccine therapy, we hope to increase awareness and improve recognition to better outcomes for these patients.

Project description: Five hundred CAYA gliomas will be screened for RRD. RRD tumours accumulate mistakes in repeated sequences, called microsatellite instability (MSI). Using new techniques to measure the frequency of MSI throughout the genome, patients with RRD can be accurately identified. Machine learning will be used to study the MRIs of >2000 gliomas to identify unique imaging characteristics. Finally, using the most common locations of MSI, a vaccine will be developed as a novel agent to treat these tumours.

Future impact: Early recognition would enable the patient to be placed on therapy tailored to RRD-tumours. This has the potential to be highly rewarding as newly available agents have shown increased efficacy against RRD. The patient would start a surveillance protocol to screen for other types of cancer. First degree family members would be screened for RRD, and if found would start surveillance to promote early detection of cancer. This will not only benefit the patient, but potentially the entire family.

Principal Investigator

Uri Tabori , The Hospital For Sick Children

Team Members

Cynthia Hawkins, The Hospital For Sick Children

Jane Barron, Memorial University

Sunit Das, St. Michael’s Hospital

Sidney E. Croul, Dalhousie University

Birgit Ertl-Wagner, The Hospital for Sick Children

Andrew Gao, University Health Network

Normand J Laperriere, Princess Margaret Cancer Centre

Julia Keith, Sunnybrook Health Sciences Centre

Farzad Khalvati, The Hospital for Sick Children

Derek Tsang, Princess Margaret Cancer Centre – UHN

Partners and Donors

Canadian Cancer Society

Canadian Institutes of Health Research