Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
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Previously we have reported the presence of simian virus 40 DNA in 56% of diffuse large B-cell lymphomas in Tunisia. Here, we investigated the relationship between the status of simian virus 40 and t(14;18) translocation, germinal center status, and P53 and BCL2 expression to assess the clinical and biological relevance of simian virus 40 presence in diffuse large B-cell lymphomas. Therefore, we evaluated by immunohistochemistry the expression patterns of CD10, BCL6, MUM1, BCL2, and P53 in 86 diffuse large B-cell lymphomas (48 simian virus 40-positive and 38 simian virus 40-negative cases). The t(14;18) translocation was investigated by polymerase chain reaction. Immunostaining patterns for CD10, BCL6, and MUM1 were used to subclassify diffuse large B-cell lymphoma cases as germinal center or non-germinal center phenotypes. Germinal center phenotype, t(14;18), P53, and BCL2 expression were found in 71, 30, 55, and 65% of cases, respectively. Interestingly, germinal center phenotype, t(14;18), and P53 accumulation were found to be more frequent in simian virus 40-positive cases than in simian virus 40-negative ones (81, 44, 69 vs 58, 13, 37%; P=0.018, 0.002, and 0.003, respectively). However, there were no correlations between the presence of simian virus 40 and the expression of CD10, BCL6, MUM1 and BCL2, patient's age and gender, clinical stage, or the International Prognosis Index. Multivariate logistic regression analyses revealed that the germinal center phenotype, P53 accumulation, and t(14;18) were independent factors for simian virus 40 association (P=0.029, 0.006, and 0.014, respectively). There were no significant differences in overall survival regarding P53, BCL2, or t(14;18) status. However, patients with germinal center phenotype or low International Prognosis Index scores displayed a significantly better survival than those with non-germinal center phenotype or high International Prognosis Index scores (P=0.003 and 0.0001, respectively). These two prognosis factors remain independent in multivariate analyses (P=0.001 and <0.0001, respectively). Interestingly, among patients with germinal center phenotype, simian virus 40-positive subgroup displayed a significantly shorter survival than simian virus 40-negative subgroup (P=0.034). In summary, these findings support a role of simian virus 40 in the pathogenesis of diffuse large B-cell lymphomas. On other hand, they suggest that a significant proportion of diffuse large B-cell lymphoma cases with germinal center phenotype may result from early transformation by simian virus 40, mainly those harboring the t(14;18). Modern Pathology (2008) 21, 282-296; doi:10.1038/modpathol.3800993; published online 28 December 2007.
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PMID:Presence of simian virus 40 in diffuse large B-cell lymphomas in Tunisia correlates with germinal center B-cell immunophenotype, t(14;18) translocation, and P53 accumulation. 1816

The classification of primary cutaneous large B-cell lymphoma (PCLBCL) is based on standard morphology, immunohistochemistry, and clinical presentation. There are two major subtypes in the current WHO-EORTC classification: follicle center lymphoma and diffuse large B-cell lymphoma, leg-type (DLBCL-LT). The goals of this study were to examine a series of DLBCLs to determine (1) whether the immunohistochemical paradigm of germinal center B-cell and non-germinal center B-cell types of systemic DLBCL could be applied to PCLBCL; (2) whether application of the newly described germinal center B-cell marker, human germinal center-associated lymphoma (HGAL) also discriminates between these types as a further support for germinal center B-cell origin for primary cutaneous center lymphoma; and (3) whether any of these biologic markers were of prognostic significance. To this end, 32 cases of diffuse PCLBCL (22 primary cutaneous follicular center lymphomas and 10 DLBCL-LT) were classified based on the WHO-EORTC criteria and studied for expression of CD20, BCL2, BCL6, CD10, MUM-1, and HGAL by immunohistochemistry. Results were correlated with clinical features. HGAL and BCL6 expression and germinal center B-cell phenotype were associated with primary cutaneous follicular center lymphoma. The combination of HGAL and BCL6 positivity had the highest sensitivity (88%) and specificity (100%) for predicting subtype compared to either marker alone. Both HGAL and BCL6 were associated with the germinal center B-cell phenotype. The correlation of HGAL expression with the germinal center B-cell phenotype demonstrates the role of this marker in the classification of cutaneous large B-cell lymphomas. BCL6 expression was the only immunohistochemical marker associated with overall survival. Characterizing PCLBCLs with markers of B-cell maturation stage is a useful framework for studying, classifying, and clinically stratifying these lymphomas.
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PMID:Expression of HGAL in primary cutaneous large B-cell lymphomas: evidence for germinal center derivation of primary cutaneous follicular lymphoma. 1826 83

Diffuse large B-cell lymphomas (DLBCL) can be subdivided into germinal centre (GC)-like and non-GC-like subtypes by CD10, BCL6 and MUM1/IRF4 status. We previously reported that patients with severe rheumatoid arthritis (RA) are at increased risk of non-GC DLBCL. This study examined a new GC-marker, human germinal-centre-associated lymphoma (HGAL) protein, in RA-DLBCL. Of 111, 38 (34%) DLBCL were HGAL-positive and showed less disseminated disease and a tendency toward improved overall survival compared to HGAL-negative cases. This supports that a majority of RA-DLBCL are of non-GC origin, indicating a specific role for activated peripheral B cells in the pathogenesis of RA-DLBCL.
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PMID:Expression of the human germinal-centre-associated lymphoma protein in diffuse large B-cell lymphomas in patients with rheumatoid arthritis. 1832 68

The characteristics of de novo diffuse large B-cell lymphoma (DLBCL) with translocation of c-myc and immunoglobulin (Ig) genes (c-myc/Ig DLBCL), were investigated in 13 cases of c-myc/Ig DLBCL. Immunohistochemistry revealed five cases were positive for CD10 and BCL6 expression (CD10(+)/BCL6(+)), five cases of CD10(-)/BCL6(+)/MUM1(-), one case of CD10(-)/BCL6(+)/MUM1(+) and two cases of CD10(-)/BCL6(-)/MUM1(+) expression, indicating 10 cases of germinal center B-cell DLBCL and three cases of non-germinal center B-cell DLBCL. Ongoing mutation of the Ig heavy chain gene variable region (IgH-V) was found in two cases with CD10 and BCL6 expression and one case showing CD10(-)/BCL6(+)/MUM1(-) expression. These three cases of ongoing mutation of the IgH-V gene did not express BCL2, unlike those without ongoing mutation. These results suggest a heterogeneous immunophenotype and genotype for c-myc/Ig DLBCL, with CD10(-)/BCL6(+)/MUM1(-) cases the most frequent.
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PMID:Characterization of de novo diffuse large B-cell lymphoma with a translocation of c-myc and immunoglobulin genes. 1846 Apr 3

We studied the clinicopathologic features and treatment outcome of patients with breast diffuse large B-cell lymphoma. As to the cellular immunophenotype, CD5 was detected in two patients, CD10 in 4, BCL2 in 20, BCL6 in 11, and MUM-1 in 17. The 5-year progression-free survival was 77% and the 5-year overall survival was 87%. Patients with the germinal center B-cell (GCB) type had a significantly better prognosis than those with the non-GCB type. The combination of anthracycline-containing chemotherapy and/or involved-field radiotherapy produced a relatively good prognosis. However, it is a heterogeneous disease with regard to histological type and pathological state.
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PMID:Clinicopathologic features and treatment outcome of primary breast diffuse large B-cell lymphoma. 1849 56

Follicular lymphoma (FL) is one of the most common subtypes of non-Hodgkin lymphoma and frequently transforms to diffuse large B-cell lymphoma (DLBCL). To clarify some aspects of the natural history of FL, we retrospectively examined 43 consecutive patients who had DLBCL with pre- or coexisting FL grade 1 or 2. The patients comprised 22 men and 21 women with a median age of 53 years. Most of the patients (34/43) showed advanced-stage (III or IV) disease initially. We examined both FL and DLBCL components morphologically, immunohistochemically, and by interface fluorescence in situ hybridization (FISH: IGH/BCL2 fusion, BCL6 translocation) analysis. Most of the DLBCLs were classified as the centroblastic subtype, with two exceptions of the anaplastic subtype. Immunohistochemical analysis of both the FL and DLBCL components revealed the following respective positivity rates: CD20 100%/100%, CD10 86%/66%, Bcl-2 96%/91%, Bcl-6 84%/88%, MUM1 16%/34%, CD30 0%/20%, CD138 0%/0%, and CD5 0%/3%. Loss of CD10 (6/36, 17%) and gain of MUM1 (7/28, 25%) and CD30 (5/21, 24%) through transformation were not infrequent. High positivity rates for Bcl-2 and Bcl-6 were maintained throughout transformation. Among the DLBCLs, 84% were classified as the germinal center B-cell phenotype (GCB) and 16% as non-GCB in accordance with the criteria of Hans et al. IGH/BCL2 fusion was detected by FISH in 89% of FLs and 82% of DLBCLs. BCL6 translocation was detected in 1/6 (17%) DLBCLs without IGH/BCL2 fusion. Thus, although the morphological features and FISH results for DLBCL were consistent with transformed FL, the immunophenotype showed wide heterogeneity.
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PMID:Diffuse large B-cell lymphoma after transformation from low-grade follicular lymphoma: morphological, immunohistochemical, and FISH analyses. 1854 5

Dual IgH/BCL2 and BCL6 translocations are rarely observed in B-cell non-Hodgkin lymphomas (B-NHLs). We investigated the morphologic, phenotypic, and cytogenetic spectrum of B-NHL with such dual translocations. Dual IgH/BCL2 and BCL6 translocations were detected in follicular lymphomas (FLs) and diffuse large B-cell lymphomas (DLBCLs), representing 6.1% of 132 B-NHLs in our series, including 6 (11%) of 56 FLs (grades 1, 2, and 3a) and 2 (3%) of 76 DLBCLs; 33% of FLs with dual translocations had variant morphologic features. All dual-translocation FLs were CD10+/BCL6+/BCL2+/MUM1-, and the DLBCLs demonstrated "activated" germinal center (CD10+/BCL6+/MUM1+) and non-germinal center (CD10-/BCL6+/MUM1+) phenotypes. BCL6 translocations in all cases involved nonimmunoglobulin genes/loci. Mean chromosome abnormalities in dual-translocation FLs and DLBCLs did not differ from IgH/BCL2 FLs and DLBCLs. Detection of dual translocations predominantly in low-grade FLs suggests that BCL6 abnormalities are acquired early in the histologic evolution of a subset of IgH/BCL2-associated FLs.
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PMID:The spectrum of B-cell non-Hodgkin lymphomas with dual IgH-BCL2 and BCL6 translocations. 1862 87

Diagnosis and classification of aggressive mature B-cell lymphoma with atypical morphology remains a challenge. To identify factors that may contribute to the atypical morphology, we selected eight such cases and evaluated their morphologic, immunophenotypic and cytogenetic features and clinical outcomes. The neoplastic cells showed a diffuse monotonous infiltrating pattern with a spectrum of morphology including: 1) L1 lymphoblastic; 2) centroblastic; 3) immunoblastic; and 4) mixed centroblastic and immunoblastic. The lymphoma cells in most cases were positive for CD10 and/or BCL6, and showed BCL2 expression. 6 of 8 cases showed C-MYC rearrangements, and interestingly, all 6 cases demonstrated a proliferation index of < or =90%. 3 of the 6 cases also demonstrated t(14;18). Clinical follow-up indicated that aggressive mature B-cell lymphoma may benefit from more intensified chemotherapeutic regimens used for BL. Our study suggests that aggressive mature B-cell lymphoma with atypical morphology may be another "grey zone lymphoma" lying in the spectrum between Burkitt lymphoma and diffuse large B-cell lymphoma.
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PMID:C-MYC rearrangements are frequent in aggressive mature B-Cell lymphoma with atypical morphology. 1878 24

Burkitt lymphoma (BL) has a characteristic clinical presentation, morphology, immunophenotype and primary chromosomal aberration, that is, the translocation t(8;14)(q24;q32) or its variants. However, diagnostic dilemmas may arise in daily practice due to overlap of BL with subsets of other aggressive, mature B-cell lymphomas such as diffuse large B-cell lymphomas (DLBCL). Recently, two gene expression studies have described a distinct molecular profile for BL, but also showed the persistence of some cases intermediate between BL and DLBCL. An alternative approach to define BL is to consider (cyto)genetic data, in particular chromosomal abnormalities other than the t(8;14) or its variants. In this review the 'Mitelman Database of Chromosome Aberrations in Cancer,' harboring the majority of all published neoplasia-related karyotypes, was explored to define a cytogenetic profile of 'true' BL. This core subset of BL showed a very low complexity of chromosomal abnormalities with 40% of the cases having the IG-MYC fusion as the sole abnormality. In the remaining cases, additional recurrent but partially exclusive abnormalities included gains at chromosomes 1q, 7 and 12, and losses of 6q, 13q32-34 and 17p. Within the core subset, no differences were found between pediatric and adult patients. In addition, the genetic profile of the core subset was significantly different from BL with an 8q24 breakpoint not affecting one of the three immunoglobulin loci, BL with a translocation involving 18q21/BCL2, 3q27/BCL6 or 11q13/BCL1, additionally to a breakpoint at 8q24/MYC, and from other morphological types of lymphomas with an 8q24/MYC breakpoint. These groups showed a higher cytogenetic complexity than the core subset of BL. BL without a detectable 8q24/MYC breakpoint might be heterogeneous and deserves further studies. We suggest that, concordant with the WHO classification to be published in 2008, the diagnosis of BL should be restricted to cases with expression of CD10 and BCL6, absence or very weak expression of BCL2 protein, a homogeneously very high proliferation index and a proven IG-MYC translocation without evidence of a chromosomal translocation typical for other lymphoma entities. In addition, a high number of nonspecific cytogenetic abnormalities should suggest need for a critical review of the diagnosis of BL.
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PMID:Translocations involving 8q24 in Burkitt lymphoma and other malignant lymphomas: a historical review of cytogenetics in the light of todays knowledge. 1892 40

Follicular lymphoma (FL) is a morphologically and genetically well-characterized B-cell non-Hodgkin lymphoma that can show predominantly follicular, combined follicular and diffuse, or predominantly diffuse growth patterns. Although approximately 85% of FLs harbor the translocation t(14;18)(q32;q21) and consistently display a follicular growth pattern, predominantly diffuse FLs are less well characterized on the phenotypical, molecular, and clinical level. We studied 35 predominantly diffuse FL by immunohistochemistry, classical chromosome banding analysis, fluorescence in situ hybridization (FISH), and gene expression profiling. A total of 28 of 29 analyzable cases lacked t(14;18), and 27 of 29 cases revealed a unifying chromosomal aberration, a deletion in 1p36. Morphologically, 12 FLs were grade 1 and 23 were grade 2, and the immunophenotype with frequent expression of CD10, BCL6, and CD23 was in line with a germinal center B-cell phenotype. The gene expression profiles of 4 predominantly diffuse FLs fell into the spectrum of typical FL, with a unique enrichment of specific gene signatures. Remarkably, patients with diffuse FL frequently presented with low clinical stage and large but localized inguinal tumors. These results suggest that predominantly diffuse FL represent a distinct subtype of t(14;18)-negative nodal FL with a unifying genetic alteration (deletion of 1p36) and characteristic clinical features.
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PMID:A distinctive subtype of t(14;18)-negative nodal follicular non-Hodgkin lymphoma characterized by a predominantly diffuse growth pattern and deletions in the chromosomal region 1p36. 1897 8


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