Rearrangements of the BCL6 gene in diffuse large cell non-Hodgkin's lymphoma

Coco, Francesco Lo; Ye, Ben Haobin; Lista, Florigio; Corradini, Paolo; Offit, Kenneth; Knowles, DM; Chaganti, RS; Dalla‐Favera, Riccardo

doi:10.1182/blood.v83.7.1757.1757

Cited by 257 publications

(58 citation statements)

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“…The incidence of BCL6 rearrangement in untreated diffuse aggressive lymphoma seemed to be lower in the present study than in other studies Lo Coco et al, 1994;Otsuki et al, 1995) (Table V). However, in relapsed cases in which primary biopsied material was not available for molecular analysis, the incidence was significantly higher, and the overall incidence in diffuse aggressive lymphomas examined in this study was 21 .…”

Section: Discussioncontrasting

confidence: 77%

Rearrangement of the BCL6 gene in B‐cell lymphoid neoplasms: comparison with lymphomas associated with BCL2 rearrangement

et al. 1996

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We report a series of B-cell neoplasms with regard to rearrangement of the BCL6 gene on chromosome band 3q27. Southern blot analysis using probes from the major translocation cluster (MTC) region of the BCL6 revealed rearrangement in 21/197 patients (10.7%) with B-cell neoplasms studied at presentation, and 11/25 patients (44%) first studied at relapse. In non-Hodgkin's lymphoma (NHL) studied at diagnosis, rearrangements of the BCL6 gene were not closely associated with a specific histopathologic subtype but distributed in subcategories in the Working Formulation. The incidence in follicular lymphoma was 12.1%, with significantly higher frequency in mixed and large cell subtypes, and that in diffuse aggressive lymphoma was 14.1%. Comigration analysis using probes from the immunoglobulin genes revealed association of the BCL6 gene with one of the three immunoglobulin loci in 9/25 cases analysed. A comparative study between NHL associated either with BCL2 or BCL6 rearrangement showed that advanced disease and bone marrow involvement were more frequent in BCL2(+) NHL. In contrast, extranodal involvement was more frequently observed in the BCL6(+) NHL. The survival curve of BCL6(+) NHL was characterized by a rapid decline followed by a plateau. Of the total of 32 BCL6(+) patients, six carried both BCL2 and BCL6 rearrangements; five of these six showed clinicopathological properties characteristic of follicular lymphoma, suggesting that the presence of the two genetic abnormalities does not necessarily have synergistic effects on malignant phenotypes. The high level of BCL6 expression in follicular lymphoma cell lines carrying a BCL2 rearrangement suggests that the deregulated BCL2 gene may have an effect on the development of genetic abnormalities of the BCL6 gene. The present study suggests that BCL6 gene rearrangement is primarily involved in large cell lymphoma irrespective of growth pattern of neoplastic cells, and that BCL6(+)BCL2(-) NHL could be curable with modern intensive chemotherapy.

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Section: Discussioncontrasting

confidence: 77%

Rearrangement of the BCL6 gene in B‐cell lymphoid neoplasms: comparison with lymphomas associated with BCL2 rearrangement

et al. 1996

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“…Several surveys of non-Hodgkin's lymphoma (NHL) panels reported similar frequencies in various NHL subtypes, i.e. 30-40% in DLCL, 5-14% in follicular lymphoma (FL;Ye et al, 1993a;Bastard et al, 1994;Lo Coco et al, 1994;Ohno et al, 1994;Otsuki et al, 1995) and 20% in acquired immune deficiency syndrome (AIDS)-associated DLCL (Gaidano etal., 1994). In DLCL, cases with BCL6 rearrangements have distinct clinical features including a favorable prognosis .…”

Section: Introductionmentioning

confidence: 99%

Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma.

et al. 1995

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The BCL6 gene codes for a zinc‐finger transcription factor and is involved in chromosomal rearrangements in 30–40% of diffuse large‐cell lymphoma (DLCL). These rearrangements cluster within the 5′ regulatory region of BCL6 spanning its first non‐coding exon. 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. In all three cases, the breakpoints were mapped within the IgH switch region and the BCL6 first intron, leading to the juxtaposition of part of the IgH locus upstream and in the same transcriptional orientation to the BCL6 coding exons. An analysis of cDNA clones showed that these recombinations generate chimeric IgH‐BCL6 transcripts which initiated from IgH germline transcript promoters (I mu or I gamma 3), but retain a normal BCL6 coding domain. In the tumor cell line, the chimeric I gamma 3‐BCL6 allele, but not the germline BCL6 gene, was transcriptionally active and produced a normal BCL6 protein. These findings indicate that t(3;14) translocations alter BCL6 expression by promoter substitution and imply that the consequence of these alterations is the deregulated expression of a normal BCL6 protein.

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“…BCL6 gene rearrangements have been demonstrated in a considerable proportion of diffuse large cell lymphoma frequently arising at extranodal sites and displaying a favourable prognosis and less frequently in follicular lymphoma bearing the t(14;18) (Bastard et al, 1994;Lo Coco et al, 1994;Otsuki et al, 1995). It is also interesting to note that two cases with BCL6 gene rearrangement reported by Horsman et al (1995) were composite lymphomas with a monocytoid B-cell component.…”

Section: Discussionmentioning

confidence: 97%

“…Rearrangement of the BCL6 proto-oncogene located on 3q27 has been detected in 29-45% of diffuse large cell lymphoma and 6-14% of follicle centre cell lymphoma (Bastard et al, 1994;Lo Coco et al, 1994;Otsuki et al, 1995), but rarely in other conditions such as HIV-associated Hodgkin's disease (Offit et al, 1989), HIV-associated lymphoid hyperplasia (Schlegelberger & Grote, 1993), or chronic lymphocytic leukaemia (Horsman et al, 1995).…”

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BCL6 gene rearrangements also occur in marginal zone B‐cell lymphoma

Dierlamm

Pittaluga²,

Stul

et al. 1997

Br J Haematol

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Summary.Marginal zone B-cell lymphoma (MZBCL) represents a distinct subtype of B-cell non-Hodgkin's lymphoma (NHL) which has been recently recognized and defined as a disease entity. Cytogenetically, these lymphomas reveal a high prevalence of trisomy 3, and recent data obtained by comparative genomic hybridization indicate that the chromosomal regions 3q21-23 and 3q25-29 might be of particular pathogenetic significance. We identified structural chromosomal abnormalities involving the region 3q27 and rearrangements of the BCL6 proto-oncogene in three out of 34 (9%) well-defined cases of extranodal, nodal and splenic MZBCL using cytogenetic analysis, Southern blot, and fluorescence in situ hybridization (FISH). All three cases were characterized by a t(3;14)(q27;q32). Two of them showed additional chromosomal abnormalities including trisomy 3, which was found in one case. The patients displayed extranodal disease and did not demonstrate any striking clinical and histological differences when compared with MZBCL lacking BCL6 rearrangement. The present study for the first time demonstrates the occurrence of t(3;14)/BCL6 gene rearrangement in MZBCL, thus suggesting a role of the BCL6 proto-oncogene in the pathogenesis of MZBCL.

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Rearrangements of the BCL6 gene in diffuse large cell non-Hodgkin's lymphoma

Cited by 257 publications

References 0 publications

Rearrangement of the BCL6 gene in B‐cell lymphoid neoplasms: comparison with lymphomas associated with BCL2 rearrangement

Rearrangement of the BCL6 gene in B‐cell lymphoid neoplasms: comparison with lymphomas associated with BCL2 rearrangement

Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma.

BCL6 gene rearrangements also occur in marginal zone B‐cell lymphoma

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