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Frequent mutation of the 5' noncoding region of the BCL-6 gene in acquired
immunodeficiency syndrome-related non-Hodgkin's lymphomas
G Gaidano, A Carbone, C Pastore, D Capello, A Migliazza, A Gloghini, S Roncella, M Ferrarini, G Saglio and R Dalla-Favera
Dipartimento di Scienze Mediche, Universita di Torino, Novara, Italy.
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.
Volume 89,
Issue 10,
pp. 3755-3762,
05/15/1997
Copyright © 1997 by The American Society of Hematology
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