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100-570 West 7th Avenue Vancouver, B.C. Canada V5Z 4S6 Tel: (604) 707-5803 Fax: (604) 876-3561 http://bioinformatics.ubc.ca EXIT SEMINAR Calvin Lefebvre B.Sc. , University of Toronto, 2011 DATE: May 8, 2015 12 noon – 1 pm LOCATION: Dorothy Lam Boardroom 675 West 10th Avenue Cis-Regulatory Somatic Mutations and Gene-Expression Alteration in B Cell Lymphomas Abstract: Substantial progress has been achieved in characterizing protein coding regions for cancer genomes, with large contributions coming from TCGA and the ICGC. In order to obtain a complete mutational profile of cancer genomes, the whole genome must be analyzed for two reasons: a large proportion of somatic mutations are within the noncoding region and 80% of the human genome is estimated to have some biological functionality. The dramatic cost reduction afforded by next generation sequencing has now made it tractable to sequence entire cancer genomes, allowing mutational profiling of the functional loci in the non-coding regions, such as cis-regulatory elements. Recent cancer genomic studies observed somatic mutations within cis-regulatory elements have the capacity to deregulate gene expression, but their impact remains underexplored. Initial attempts to prioritize cis-regulatory mutations did not incorporate RNA-Seq. We used 84 B cell lymphoma samples to address this limitation by prioritizing disruptive cisregulatory mutations based on their potential to be the cause of observable cascading expression changes throughout biological networks. BCL6, ROBO1, GNA13, HAS2 and MYC were dysregulated genes targeted with somatic mutations through different mechanisms. Mutations either targeted the genes directly (protein coding mutations), indirectly (cis-regulatory mutations) or both. Our analyses demonstrates the importance of identifying genomically altered cisregulatory elements, along with gene expression data, to interpret the mutational landscapes of cancers. Supervisor: Dr. Sohrab Shah, Pathology and Computer Science, UBC