Grant: Master's Award: Canada Graduate Scholarships

Diffuse large B-cell lymphoma (DLBCL), the most common blood cancer, fails to respond to standard chemotherapy in 15% of patients. There is a need to identify patients with potentially chemo-resistant disease so that they may be offered alternative, possibly experimental, therapy. All of the currently known cancer-causing mutations in DLBCL biopsy samples affect the approximately 1.5% of the human genome that codes for proteins. Although most mutations found in lymphoma samples involve the 98.5% of the genome that does NOT code for proteins, the potential causative role of these “non-coding” mutations in lymphoma development and persistence is not known. We hypothesize that mutations in non-coding regions can drive DLBCL by affecting the binding of key regulatory proteins to DNA and that this ultimately changes the expression of critical genes. In this research, we aim to identify novel “driver” mutations and elucidate their causative role in DLBCL. We will do this by performing DNA sequencing and gene expression assays on DLBCL biopsy specimens to identify mutations that specifically affect the binding of key regulatory proteins and the expression of nearby genes. In this manner, we will uncover novel disease mechanisms in DLBCL that will inform better, more precise use of targeted anti-cancer drugs.