BCL-6 in aids-related lymphomas: pathogenetic and histogenetic implications.
AIDS-related non-Hodgkin's lymphomas (AIDS-NHL) are classified into Burkitt's lymphoma, diffuse large cell lymphoma (DLCL), and body cavity based lymphoma. The molecular pathogenesis of AIDS-NHL is complex and involves the genetic alteration of several cancer related genes, including the BCL-6 proto-oncogene. BCL-6 encodes a zinc finger transcription factor which is selectively expressed by germinal center (GC) B-cells, but not by pre-GC or post-GC B-cells. Genetic alterations of BCL-6 occur frequently among B-cell NHL and comprise gross rearrangements as well as small mutations of the 5' noncoding region of the gene. Gross rearrangements of BCL-6 among AIDS-NHL cluster with 20% AIDS-DLCL. Conversely, mutations of the 5' noncoding region of BCL-6 occur at sustained frequency throughout the clinico-pathologic spectrum of AIDS-NHL and represent the most common genetic alteration presently detectable in these lymphomas. The frequency of BCL-6 mutations, as well as their location in the proximity of the BCL-6 regulatory regions, suggest that they may play a pathogenetic role in AIDS-related lymphomagenesis. Beside their pathogenetic implications, the occurrence of BCL-6 mutations among AIDS-NHL bears histogenetic relevance because BCL-6 mutations are regarded as a marker of B-cell transition through the GC. Thus, it is conceivable that a large fraction of AIDS-NHL is histogenetically related to GC or post-GC B-cells. This notion is further confirmed by the observation that AIDS-NHL frequently express the BCL-6 protein, which stains selectively GC B-cells throughout B-cell differentiation.
Gaidano
G
G
Department of Medical Sciences, University of Torino at Novara, Italy. gaidano@med.no.unipmn.it
Capello
D
D
Gloghini
A
A
Pastore
C
C
Migliazza
A
A
Quattrone
S
S
Savinelli
F
F
Buonaiuto
D
D
Cilia
A M
AM
Perin
T
T
Pasqualucci
L
L
Canzonieri
V
V
Saglio
G
G
Dalla-Favera
R
R
Carbone
A
A
D015321:Gene Rearrangement; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000235:genetics*; D009154:Mutation; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D014157:Transcription Factors / Q000235:genetics; D016335:Zinc Fingers
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors