Involvement of the bcl-6 gene in AIDS-related lymphomas.
BACKGROUND
Non-Hodgkin's lymphoma (NHL) represents a major complication of AIDS. Systemic AIDS-related NHLs (AIDS-NHLs) derive from B cells and are classified into four distinct groups, including small noncleaved-cell lymphoma (SNCCL), diffuse large-cell lymphoma (DLCL), anaplastic large-cell lymphoma (ALCL), and body-cavity-based lymphoma (BCBL). The molecular pathogenesis of AIDS-NHL is characterized by the association of specific genetic lesions with distinct AIDS-NHL categories. Genetic lesions of AIDS-NHL involve proto-oncogenes (c-myc, Ras), tumor suppressor loci (p53, 6q), and viral infection (Epstein-Barr virus, human herpesvirus type 8).


METHODS
The aim of this work was to define the involvement of the bcl-6 gene in AIDS-related lymphomagenesis by investigating the distribution of bcl-6 structural alterations throughout the pathologic spectrum of AIDS-NHL. Both gross rearrangements and mutations in the 5' noncoding regions of the gene were investigated.


RESULTS
Gross rearrangements of bcl-6 are confined to a fraction of AIDS-DLCL cases among AIDS-NHLs. Conversely, mutations of the 5' noncoding regions of bcl-6 are detected in a large proportion of AIDS-SNCCLs, AIDS-DLCLs and AIDS-ALCLs independent of the concomitant presence of bcl-6 rearrangements.


CONCLUSIONS
Mutations of the 5' noncoding regions of bcl-6 represent the most frequent genetic lesion presently detectable among systemic AIDS-NHLs. The frequency of these mutations and their location in the proximity of bcl-6 regulatory regions suggest that they may play a role in AIDS-related lymphomagenesis.
Gaidano
G
G
Dipartimento di Scienze Mediche, Università di Torino, Novara, Italy.
Pastore
C
C
Capello
D
D
Migliazza
A
A
Gloghini
A
A
Saglio
G
G
Carbone
A
A
Dalla-Favera
R
R
D004268:DNA-Binding Proteins / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000235:genetics*; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors