Mantle cell lymphoma (MCL) is a rare cancer that derives from B lymphocytes in the periphery (mantle zone) of the germinal centre. MCL is most often diagnosed at stage 3 or 4 and is typically aggressive although some patients have an indolent form of the disease. Only 30-40% of patients with advanced disease achieving a complete response to frontline treatments (R-bendamustine). Heterogeneous clinical response is partially attributable to observable variations in morphology, immunophenotype and proliferative capacity; however, there is little known about the relationship between genetic features and variation in phenotype or response to specific treatment regimens. Through a meta-analysis of in-house and existing exome sequencing data, our group has identified multiple novel driver mutations in MCL including some that associate with high or low proliferation. To more completely ascertain the mutations that lead to lymphomagenesis in MCL, we are performing an integrative proteogenomic characterization of MCL tumours using a combination of whole genome sequencing, RNA-seq and shotgun proteomics. We are using these data to identify novel coding and non-coding (i.e. regulatory) driver mutations that affect the natural history of MCL including treatment response.