Involvement of the bcl-6 gene in AIDS-related lymphomas

Background: Non-Hodgkin's lymphoma (NHL) represents a major complication of AIDS. Systemic AIDS-related NHLs (AIDS-NHLs) derive from B cells and are classified into four distinct groups, including small noncleaved-cell lymphoma (SNCCL), diffuse large-cell lymphoma (DLCL), anaplastic large-cell lymphoma (ALCL), and body-cavity-based lymphoma (BCBL). The molecular pathogenesis of AIDS-NHL is characterized by the association of specific genetic lesions with distinct AIDS-NHL categories. Genetic lesions of AIDS- NHL involve proto-oncogenes (c-myc, Ras), tumor suppressor loci (p53. 6q), and viral infection (Epstein-Barr virus, human herpesvirus type 8). Design: The aim of this work was to define the involvement of the bcl-6 gene in AIDS- related lymphomagenesis by investigating the distribution of bcl-6 structural alterations through out the pathologic spectrum of AIDS-NHL. Both gross rearrangements and mutations in the 5' noncoding regions of the gene were investigated. Results: Gross rearrangements of bcl-6 are confined to a fraction of AIDS-DLCL cases among AIDS-NHLs. Conversely, mutations of the 5' noncoding regions of bcl-6 are detected in a large proportion of AIDS- SNCCLs, AIDS-DLCLs and AIDS-ALCLs independent of the concomitant presence of bcl-6 rearrangements. Conclusions: Mutations of the 5' noncoding regions of bcl-6 represent the most frequent genetic lesion presently detectable among systemic AIDS-NHLs. The frequency of these mutations and their location in the proximity of bcl-6 regulatory regions suggest that they may play a role in AIDS-related lymphoma-genesis.