title: Frequent mutation of the 5' noncoding region of the BCL-6 gene in acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas.
abstract: Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (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 lymphoma (ALCL) and body-cavity-based lymphoma (BCBL) represent less frequent AIDS-NHL types. The molecular pathogenesis of AIDS-NHL is characterized by distinct genetic pathways, including chromosomal rearrangements of c-MYC and BCL-6 in AIDS-BL and AIDS-DLCL, respectively. In addition 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 panel representative of all the AIDS-NHL subtypes. Forty-three AIDS-NHL were analyzed for mutations in the first exon-first intron boundary region of BCL-6. Mutations were detected in all categories of AIDS-NHL (25 of 43 cases; 58%), including 12 of 20 AIDS-BL, 10 of 15 AIDS-DLCL, two of three AIDS-ALCL, and one of five of AIDS-BCBL. BCL-6 mutations occurred independent of BCL-6 rearrangements and presence of other genetic lesions frequently associated with AIDS-NHL. These results indicate that mutations of BCL-65' noncoding regions represent the most common 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-related lymphomagenesis.
authors.affiliation: Dipartimento di Scienze Mediche, Universita di Torino, Novara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Gaidano
authors.forename: A
authors.initials: A
authors.lastname: Carbone
authors.forename: C
authors.initials: C
authors.lastname: Pastore
authors.forename: D
authors.initials: D
authors.lastname: Capello
authors.forename: A
authors.initials: A
authors.lastname: Migliazza
authors.forename: A
authors.initials: A
authors.lastname: Gloghini
authors.forename: S
authors.initials: S
authors.lastname: Roncella
authors.forename: M
authors.initials: M
authors.lastname: Ferrarini
authors.forename: G
authors.initials: G
authors.lastname: Saglio
authors.forename: R
authors.initials: R
authors.lastname: Dalla-Favera
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002051:Burkitt Lymphoma / Q000209:etiology / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000145:classification / Q000235:genetics* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000145:classification / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000209:etiology / Q000235:genetics; D017728:Lymphoma, Large-Cell, Anaplastic / Q000209:etiology / Q000235:genetics; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D011519:Proto-Oncogenes; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors