Biological Variants Underlying Racial Differences in Lymphoma

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DESCRIPTION (provided by applicant): Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in the US, affecting ~22,000 people/year. If untreated 92% of DLBCL die within 1 year, however, with modern combinations of chemotherapy and immunotherapy >50% of patients are cured, making DLBCL a clinically significant disease for examining cancer disparities. We discovered that black patients with DLBCL in the United States, are diagnosed at an age a decade younger age than whites (average age 53 vs. 70 years), are more likely to have advance stage disease, be uninsured or Medicaid insured, reside in the lowest socioeconomic status areas, and are less likely to have received modern chemotherapy. We confirmed these differences in age and stage in a second US population-based data set, and found blacks also had worse 5-year survival (38% vs. 46%). However, in separate studies at Emory and University of Alabama-Birmingham (UAB) and our combined study, we found again that black patients presented at a significantly younger age and still had worse survival even when the exact same treatment was given. Two biologically different subtypes of DLBCL can be identified that have different survival, Germinal center B-cell (GCB) DLBCL: 60% 5-year survival and activated B-cell (ABC) DLBCL: 35%. We propose to examine relationships between these biological variants and racial differences in DLBCL. Based on a widespread analysis of genes in DLBCL tumors and matched normal tissue, we helped identified 15 genes that are differentially mutated in ABC and GCB DLBCL and seek to determine if these differ by race. The main aims are: 1) To examine racial differences in the prevalence of ABC-like DLBCL and explore the relationships between ABC subtype, race and survival, and 2) To examine racial differences in novel genes differentially mutated in ABC-like DLBCL. We identified 433 DLBCL patients from the Emory and UAB cohort studies with available tissue blocks and clinical data. We are collecting demographic, insurance, employment, treatment, response and survival data, will construct a tissue microarray, and will perform IHC subtyping, mutation and expression profiling.