Functional characterization of MLL2 mutations in follicular and diffuse large B-cell lymphomas

Lymphomas are cancers of the immune system. Canadian cancer statistics estimated around 8,100 newly diagnosed cases and 3,300 deaths from lymphoma in 2009. Lymphomas develop as the result of errors, or mutations, in the proteins that regulate the rate of cell division. These types of mutations are found in many different cancer types; however, certain mutations are found only in a specific cancer type. When the same mutation is found in several patients of a specific cancer type, it is likely to be a cancer-causing or cancer-driving mutation. The aim of Dr. Maria Mendez-Lago’s research is to investigate the impact of mutations found in the gene MLL2 on the formation and progression of lymphomas. Her research team discovered mutations in MLL2 by using next-generation sequencing of 127 non-Hodgkin lymphoma cases. Based on the pattern and distribution of the mutations, they believe MLL2 is a new tumour suppressor that might be acting through de-regulation of gene expression. Next-generation sequencing has allowed Dr. Mendez-Lago’s team to do whole genome, exome, and transcription sequencing using limited amounts of DNA from cancer tissues – an approach that was not possible only four years ago. They are applying this technology to different applications, such as the targeted sequencing approach used to detect mutations in MLL2. MLL2 has only recently been linked to cancer, so there is a great need to study the gene in further detail to understand how mutations in this gene promote cancer. To explore the impact of these mutations, Dr. Mendez-Lago’s team will culture and study all lines similar to the cancer cells from patients. Their findings will likely determine new candidates for designing drugs to treat cancers.