ABSTRACT HIV-positive patients are at high risk for developing diffuse large B cell lymphoma (DLBCL). Despite improved patient outcomes in the era of retroviral therapy, HIV-positive DLBCL patients continue to experience inferior survival compared to their HIV-negative counterparts. While the genetic origins and prognostic factors of DLBCL are increasingly well-defined, a similar understanding of the disease in HIV+ patients has been elusive. We have carried out a preliminary genomic analysis of HIV+ DLBCL patients that revealed key differences in mutation patterns. Additionally, we found differences in a previously described gene expression signature that reflects the tumor microenvironment and is strongly associated with poor survival. In this proposal, we seek to advance our understanding of the genetic and microenvironment features underlying DLBCL in HIV+ patients, particularly as they relate to outcome. Through a combination of genomics approaches in a well-powered patient cohort, we will comprehensively define the genetic alterations, gene expression patterns and microenvironment characteristics that distinguish HIV+ DLBCLs. This work will provide an important resource for the field and indicate therapeutic targets to improve outcomes in this disease, including approaches to disrupting the nexus between the tumor and the microenvironment.

PROJECT NARRATIVE HIV-positive patients are at high risk for developing diffuse large B cell lymphoma (DLBCL) and experience worse survival rates compared to HIV-negative DLBCL patients. We propose to comprehensively examine the distinct genomic and microenvironmental factors that characterize DLBCL in the context of HIV infection. We expect that these results will indicate novel therapeutic approaches that will improve outcomes in this disease as well as serve as an important resource for the field.