IDENTIFICATION OF INHERITED GENETIC RISK FACTORS FOR CHRONIC LYMPHOCYTIC LEUKEMIA
Cassandra Garner, Martha Glenn, Rosalie Waller, Venkatesh Rajamanickam, Todd Darlington, Rob Sargent, Nicola Camp
The University of Utah, Salt Lake City, UT.
B-cell lymphoproliferative disorders (lymphoma, multiple myeloma, and leukemia) are cancers of the blood and bone marrow. Taken together, they are the 4th most common cancer. In chronic lymphocytic leukemia (CLL), peripheral B-cells become malignant and accumulate in the blood stream. As CLL progresses, the circulating tumor can invade other parts of the body, including the lymph nodes and spleen. CLL is the most common form of leukemia in adults and is often fatal. The overarching goal of our research is to further understand the molecular genetic mechanisms of CLL. We hypothesize that there are germline genetic variants (common and rare) involved in the risk of CLL. Because the identification of rare, segregating variants is best conducted by pedigree-designs, we are uniquely positioned to use our local Utah genealogical resources to both describe configurations of familial disease and identify high-risk families. Additionally, we have recently expanded our research to include both germline and tumor genomics to better our understanding of the complexity of CLL. Our preliminary analyses of whole exome data have identified coding, nonsynonymous variants in SUMO pathway genes that are shared by all affected individuals in a single high-risk pedigree. We are in the process of Sanger sequencing candidate genes in both germline and tumor DNA from individuals in this pedigree in order to better characterize the potential role of the SUMO pathway in CLL and provide additional support for our findings. This research has great potential to identify variants that can be used to better diagnose and treat CLL.