It has recently been shown that BCL-6 is involved in chromosome band 3q27 aberrations in non-Hodgkin's lymphomas (NHLs) and BCL-6 rearrangements have been detected in 34-45 per cent of diffuse large cell lymphomas with B immunophenotype.
Immunohistochemical analysis of DLCL and FL biopsy samples showed that the BCL-6 protein is detectable in these tumors independent of the presence of BCL-6 gene rearrangements.
Our results show that rearrangements of BCL-6 are present in 20% of AIDS-DLCL (5 of 24), including 2 of 8 LNCCL and 3 of 16 LC-IBPL, but in no case of AIDS-SNCCL.
In our series, which was selected on cytogenetic and molecular criteria, 50% (6 of 12) of cases with BCL6/LAZ3 rearrangement were diagnosed as diffuse, large B-cell lymphomas (DLCL).
The BCL-6 gene encoding a nuclear-located Kruppel-type zinc finger protein is rearranged in about 30% diffuse large B-cell lymphomas and is expressed predominantly in normal germinal center B cells and related lymphomas.
To determine the functional consequences of these alterations, we have analyzed the structure of the rearranged BCL6 alleles and their corresponding RNA and protein species in two DLCL biopsies and one tumor cell line which carried the t(3;14)(q27;q32) translocation involving the BCL6 and immunoglobulin heavy-chain (IgH) loci.
We report here that, in 22/30 (73%) DLCL and 7/15 (47%) follicular lymphoma (FL), but not in other tumor types, the BCL6 gene is also altered by multiple (1.4 x 10(-3) -1.6 x 10(-2) per bp), often biallelic, mutations clustering in its 5' noncoding region.
AIDS-DLCL is characterized by EBV infection in the large majority of cases and by the mutually exclusive presence of bcl-6 rearrangements and c-myc translocations in 40% of the cases.
Rearrangements and mutations of the LAZ3/BCL6 gene are the most frequent events associated with diffuse large-cell lymphoma, a particular class of non-Hodgkin's lymphomas.
The human bcl-6 gene, which is rearranged in about 30% of diffuse large B-cell lymphomas (DLCL-B), encodes for a Kruppel-type zinc finger protein of 706 amino acids.
Rearrangement of BCL6 was observed in 6.4 to 14.3% of follicular lymphomas and 28.6 to 35.5% of diffuse large cell lymphomas; regarding the latter, a Japanese series showed a lower incidence.
Breakpoints at 3q27, the site of the bcl-6 gene, appear in a broad range of B cell lymphoma histologies but are most frequently detected in follicular lymphomas lacking a t(14;18) and diffuse large cell lymphomas.
High frequency of bcl-6 gene hypermutations was found in diffuse large B-cell lymphoma of the stomach and they were independent of rearrangement of the gene as detected by Southern analysis.
Distinct heterologous 5' untranslated regions (IGH, IGL, TTF) were identified fused to the BCL6 coding domain by analysis of BCL6 cDNAs in two DLCL cases and one mixed follicular lymphoma (MxFL).