Download MSc exit seminar – Calvin

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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