Multiple genetic lesions in acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma.
Non-Hodgkin's lymphoma (NHL) develops in about 5% to 10% of acquired immunodeficiency syndrome (AIDS) patients. The vast majority of AIDS-NHL are clinically aggressive B-cell NHL that are histologically classified as small noncleaved cell lymphoma (SNCCL), large cell immunoblastic plasmacytoid lymphoma (LC-IBPL), and large noncleaved cell lymphoma (LNCCL). In an attempt to understand the molecular pathogenesis of these tumors, we have investigated the involvement of dominantly acting oncogenes (c-myc, N-, K-, H-Ras), tumor suppressor genes (p53, RB1), and Epstein-Barr virus (EBV) infection in 27 AIDS-NHL samples (16 SNCCL, 5 LC-IBP, and 6 LNCCL). The following lesions were detected in AIDS-NHL: EBV infection (10/24; 41.6%), c-myc rearrangement (19/24; 79.1%), Ras mutation (4/27; 14.8%), and p53 loss/mutation (10/27; 37.0%). These lesions are not uniformly distributed, but, rather, cluster with specific types of AIDS-NHL: EBV infection is preferentially associated with LC-IBPL (4/4; 100%), while it is present in only a fraction of SNCCL (5/16; 31.2%) and LNCCL (1/4; 25%); c-myc oncogene activation clusters with SNCCL (16/16; 100%), whereas it is less frequent in LC-IBPL (1/4; 25%) and LNCCL (2/4; 50%); p53 inactivation is restricted to SNCCL (10/16; 62.5%) and consistently associated with c-myc activation. These data show that AIDS-NHL are associated with multiple genetic lesions that involve both proto-oncogenes and tumor suppressor genes and may accumulate in the relatively short period of time (4 to 6 years) between human immunodeficiency virus infection and AIDS-NHL development. These genetic lesions differ in the various AIDS-NHL subtypes, suggesting the involvement of distinct molecular pathway.
Department of Pathology, College of Physicians & Surgeons, Columbia University, New York, NY 10032.
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Ballerini
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Gaidano
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Gong
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Tassi
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Knowles
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Dalla-Favera
D000328:Adult; D001483:Base Sequence; D015139:Blotting, Southern; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006566:Herpesviridae Infections / Q000150:complications / Q000382:microbiology; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction
D004279:DNA, Viral