FREQUENT MUTATION OF THE 5'-NONCODING REGION OF THE BCL-6 GENE IN ACQUIRED IMMUNODEFICIENCY SYNDROME-RELATED NON-HODGKINS-LYMPHOMAS

Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lympho mas (AIDS-NHL), a major source of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals, are derived from B cells and are classified into two major categories, Burkitt's lymphoma (BL) and diffuse large cell lymphoma (DLCL). Anaplastic large cell ly mphoma (ALCL) and body-cavity-based lymphoma (BCBL) represent less fre quent AIDS-NHL types. The molecular pathogenesis of AIDS-NHL is charac terized by distinct genetic pathways, including chromosomal rearrangem ents of c-MYC and BCL-6 in AIDS-BL and AIDS-DLCL, respectively. In add ition to gross rearrangements, recent evidence has suggested that BCL- 6 may also be affected by mutations of the gene 5' noncoding regions, Here we have investigated the distribution of BCL-6 mutations in a pan el representative of all the AIDS-NHL subtypes. Forty-three AIDS-NHL w ere analyzed for mutations in the first exon-first intron boundary reg ion of BCL-6. Mutations were detected in all categories of AIDS NHL (2 5 of 43 cases; 58%), including 12 of 20 AIDS-BL, 10 of 15 AIDS-DLCL, t wo of three AIDS-ALCL, and one of five of AIDS-BCBL. BCL-6 mutations o ccurred independent of BCL-B rearrangements and presence of other gene tic lesions frequently associated with AIDS-NHL. These results indicat e that mutations of BCL-6 5' noncoding regions represent the most comm on genetic alteration presently detectable in AIDS-NHL. The frequency of these mutations, as well as their location in the proximity of BCL- 6 regulatory sequences, suggest that they may play a role in AIDS-rela ted lymphomagenesis. (C) 1997 by The American Society of Hematology.