GENETIC-HETEROGENEITY OF AIDS-RELATED SMALL NON-CLEAVED CELL LYMPHOMA

AIDS-related small noncleaved cell lymphoma (AIDS-SNCCL) includes Burk itt's lymphoma (BL) and high-grade B-cell Burkitt-like lymphoma (BLL). Due to the marked polymorphism of AIDS-related non-Hodgkin's lymphoma s (AIDS-NHL), the morphologic distinction between these two types of l ymphomas is frequently controversial, although it may bear clinical re levance. Although the molecular features of AIDS-BL have been clarifie d to a certain extent, the genetic peculiarities of AIDS-BLL have not been investigated in detail. In this study we have compared morphologi c and genetic features of AIDS-BL and AIDS-BLL in a blind coded fashio n. Molecular studies were focused on the genetic lesions known to be i mplicated in AIDS-NHI, including alterations of c-MYC, BCL-6, p53, del etions of 69, as well as infection by EBV and HHV-8. Alterations of c- MYC occurred in 10/10 AIDS-BL, whereas they were restricted to 2/10 AI DS-BLL (P<0.01). Mutations of p53 were present in 5/10 AIDS-BL, wherea s they were consistently absent among AIDS-BLL (n = 10; P < 0.05). Inf ection by EBV occurred in 30% of both AIDS-BL and AIDS-BLL. Rearrangem ents of BCL-6, deletions of 6q and infection by HHV-8 scored consisten tly negative in both AIDS-BL and AIDS-BLL. Based on the genetic lesion s tested, the molecular profile of AIDS-BLL appears to be closer to th at of AIDS-related diffuse large cell lymphoma (AIDS-DLCL) than to tha t of AIDS-BL. In contrast to AIDS-BLL, however, AIDS-DLCL carried rear rangements of BCL-6 in a fraction of cases (2/9). This study, the larg est of its kind reported so far, suggests that AIDS-BL and AIDS-BLL ha ve a different molecular pathogenesis and that characterization of gen etic lesions may help to distinguish between these two lymphomas.