Grant: Scriver Family MD/PhD Studentship Award

Lymphomas, which are cancers of the immune system, are the fourth most common cancer in Canada. Some slow-growing lymphomas eventually give rise to more aggressive cancers; this transformation offers an opportunity to study how a slow growing cancer progresses into a deadlier disease. Lymphomas, and indeed all cancers, arise from cells that have been altered in ways that cause the cells to lose normal control of their growth. A common way for cancer cells to be altered is through changes in their DNA. When these DNA changes (called mutations), affect regions (called genes) that are important for the cells function, cancer can arise. Mutations that cause progression to aggressive lymphoma can be detected using a technology called DNA sequencing to find changes in the lymphoma DNA that are not present in the normal DNA from the same person. Such mutations identify new functions gained by the tumor, and can represent important opportunities for the development of therapies that target the tumor but do not harm other, non-mutant cells in the same person. Intriguingly, 11 of the 19 most frequently mutated genes are involved in packaging up the DNA so that it fits into the tiny nucleus of the cell. The manner in which the DNA is wound up is very important, because if it is not done properly, it can change the manner in which genes are interpreted by the cell. This can result in diseases. One gene, MEF2B, is mutated in up to 20 percent of lymphomas, and is thought to be involved in DNA packaging. My objective is to characterize the role of MEF2B in causing lymphoma to become more aggressive. I will investigate what role MEF2B plays in DNA packaging, how the alteration in DNA packaging caused by MEF2B mutations results in more aggressive lymphoma, and the relationship between MEF2B mutations and the health of lymphoma patients. This research may suggest new approaches to predicting patient health outcomes, selecting treatments and developing new treatments.