Bioinformatics Core Project Summary All forms of the incurable plasma cell malignancies, multiple myeloma (MM), and Waldenstrom’s macroglobulinemia (WM) emerge from a precursor condition known as monoclonal gammopathy of undermined significance (MGUS). Genetic analyses of MGUS cells have provided evidence that it is a genetically advanced lesion virtually indistinguishable from MM. The risk of conversion of MGUS to MM is approximately 1% per year. The mechanisms underlying the MGUS to MM or WM transformation are unclear. One possibility is that precancerous cells alter the bone marrow microenvironment and/or immune system to facilitate the conversion to overt malignancy. The Bioinformatics Core will provide in-depth genomic analysis of tissues from a spectrum of plasma cell dyscrasias, including invaluable serial samples of purified tumor cells and whole bone-marrow biopsies from patients with MGUS enrolled in observational clinical trials and followed over the past 20 years. The core will also analyze experimental samples obtained from Research Projects 1 and 2 of the Cancer Prevention-Interception Against MGUS Progression (CAP-MGUS Center) that aim to understand and treat premalignant changes in the plasma cells, immune system, and microenvironment in order to eliminate and/or delay the onset of malignant transformation. The Myeloma Center at the University of Arkansas for Medical Sciences (UAMS), where the core will be housed, is a unique resource for laboratory and clinical investigation of plasma cell dyscrasias with a long history of studying the biology of these diseases. The Bioinformatics Core will use innovative bioinformatics techniques in the context of a large clinically and molecularly annotated archive of primary plasma cell dyscrasias, to identify molecular correlates associated with the conversion of the benign asymptomatic MGUS to MM or WM. These discoveries will form the basis for hypotheses that will be tested in the CAP-MGUS Center projects, from which additional molecular data from experimental systems will be analyzed in the Bioinformatics Core.