Point mutations of the BCL‐6 gene in Burkitt's lymphoma

Università degli Studi di Torino, Torino, Piedmont, Italy
British Journal of Haematology (Impact Factor: 4.71). 09/1997; 99(1):168 - 170. DOI: 10.1046/j.1365-2141.1997.3573171.x


BCL-6 codes for a transcription factor implicated in chromosomal translocations of diffuse large cell lymphomas. Recent evidence indicates that BCL-6 may also be altered by mutations of its 5′ non-coding regions. In this study we have investigated the distribution of BCL-6 5′ mutations among 35 Burkitt's lymphoma cases representative of the epidemiologic variants of the disease. Mutations were detected in 6/21 (28.6%) sporadic Burkitt's lymphomas and 7/14 (50%) endemic Burkitt's lymphomas. These data expand the spectrum of B-cell non-Hodgkin's lymphomas associated with BCL-6 5′ mutations and have implications for the pathogenesis, histogenesis and clinical monitoring of Burkitt's lymphoma.

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    • "Expression of BCL6 can also be altered by somatic mutation of the 5¢ non-coding region (Migliazza et al, 1995; Capello et al, 1997; Gaidano et al, 1997; Liang et al, 1997b, 1998; Peng et al, 1999) 2 , and can occur independently of translocation. Some mutations have been shown to significantly deregulate BCL6 expression, whereas others appear functionally irrelevant (Pasqualucci et al, 1998). "
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    ABSTRACT: Diffuse large B-cell lymphomas (DLBCL) are a heterogeneous group of tumours, varying in clinical features, immunophenotype and cytogenetics. The aim of this study was to investigate the prognostic significance of BCL6 gene rearrangement at the 3q27 locus in patients with primary nodal disease, and to examine interrelationships with immunophenotype and International Prognostic Index (IPI). We have developed a fluorescent in situ hybridization (FISH)-based technique for the retrospective analysis of the effect of BCL6 gene rearrangements on survival, using nuclei extracted from paraffin-embedded tissue. FISH results were obtained in 111 presentation cases of nodal DLBCL. The IPI was calculated and each case was stained immunocytochemically for BCL6, BCL2 and CD10. 3q27 rearrangements were detected in 25% of cases. BCL2 protein and a germinal centre (GC) phenotype (defined as CD10+, BCL6+) were expressed in 56% and 41% of cases respectively. In multivariate analysis, rearrangement of 3q27 and BCL2 expression and the absence of a GC phenotype were associated with a poor prognosis. These factors can be used in conjunction with the IPI to improve risk stratification in nodal DLBCL.
    Preview · Article · Jun 2002 · British Journal of Haematology
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    Preview · Article · Mar 1998 · American Journal Of Pathology
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    ABSTRACT: Primary central nervous system lymphoma (PCNSL) is a major cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals. The precise histogenetic derivation and the molecular pathogenesis of PCNSL is poorly understood. In an attempt to clarify the histogenesis and pathogenesis of these lymphomas, 49 PCNSL (26 acquired immunodeficiency syndrome [AIDS]-related and 23 AIDS-unrelated) were analyzed for multiple biologic markers, which are known to bear histogenetic and pathogenetic significance for mature B-cell neoplasms. PCNSL associated frequently (50.0%) with mutations of BCL-6 5' noncoding regions, which are regarded as a marker of B-cell transition through the germinal center (GC). Expression of BCL-6 protein, which is restricted to GC B cells throughout physiologic B-cell maturation, was detected in 100% AIDS-unrelated PCNSL and in 56.2% AIDS-related cases. Notably, among AIDS-related PCNSL, expression of BCL-6 was mutually exclusive with expression of Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP)-1 and, with few exceptions, also of BCL-2. All but one PCNSL expressed hMSH2, which among mature B cells selectively stains GC B cells. These data suggest that PCNSL may be frequently related to GC B cells and may be segregated into two major biologic categories based on the expression pattern of BCL-6, LMP-1, and BCL-2. BCL-6(+)/LMP-1(-)/BCL-2(-) PCNSL occur both in the presence and in the absence of HIV infection and consistently display a large noncleaved cell morphology. Conversely, BCL-6(-)/LMP-1(+)/BCL-2(+) PCNSL are restricted to HIV-infected hosts and are represented by lymphomas with immunoblastic features. These data are relevant for the pathogenesis and histogenesis of PCNSL and may be helpful to segregate distinct biologic and prognostic categories of these lymphomas.
    Full-text · Article · Sep 1998 · Blood
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