Rearrangements of the BCL-6 gene in acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma: association with diffuse large-cell subtype.
Acquired immunodeficiency syndrome (AIDS)-associated non-Hodgkin's lymphomas (AIDS-NHL), a major source of morbidity and mortality among AIDS patients, are derived from B cells and can be classified into two main histologic categories, small noncleaved cell lymphoma (SNCCL) and diffuse large-cell lymphoma (DLCL). DLCL includes two histologic subsets, ie, large noncleaved cell lymphoma (LNCCL) and large cell-immunoblastic plasmacytoid lymphoma (LC-IBPL). Several studies have shown that AIDS-SNCCL is associated with the clonal accumulation of multiple genetic lesions, including Epstein-Barr virus (EBV) infection, activation of the c-MYC and RAS oncogenes, as well as inactivation of the p53 tumor suppressor gene at variable frequencies. On the contrary, the molecular pathogenesis of AIDS-DLCL is largely obscure, because no genetic lesion other than EBV infection has been specifically identified in this group. In this study, we have tested a panel of 40 AIDS-NHL for structural alterations of BCL-6, a putative proto-oncogene that is frequently altered in DLCL in the immunocompetent host. Our results show that rearrangements of BCL-6 are present in 20% of AIDS-DLCL (5 of 24), including 2 of 8 LNCCL and 3 of 16 LC-IBPL, but in no case of AIDS-SNCCL. BCL-6 rearrangements were detected both in the presence and in the absence of EBV infection of the tumor clone, but in no case were associated with activation of c-MYC or mutations of p53. These data identify a novel genetic lesion in AIDS-DLCL and corroborate the notion that lymphomagenesis in AIDS follows two distinct molecular pathways that are associated with the development of histologically distinct types of AIDS-NHL.
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
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Gaidano
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Lo Coco
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Shibata
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Levine
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Dalla-Favera
D004268:DNA-Binding Proteins / Q000235:genetics*; D015321:Gene Rearrangement; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D009154:Mutation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D011519:Proto-Oncogenes; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors