The pattern and frequency of t(14;18) translocation and immunophenotype in Asian follicular lymphoma (original) (raw)
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Anticancer research, 2009
The translocation t(14;18)IgH/BCL2 is the molecular hallmark of follicular lymphomas (FL). A subset of cases harbours translocations involving the BCL6-gene locus. This study aimed to determine the frequency of BCL2- and BCL6-translocations in FL and to identify morphological and immuno-histochemical features with respect to the presence of BCL2- and BCL6-translocations. Fluorescence-in-situ-hybridisation (FISH) was used to determine the BCL2- and BCL6-translocation status of 102 FL and these were compared to morphological and immunohistochemical parameters. Lymphomas with BCL6- and BCL2-translocations were very similar to t(14;18)-positive lymphomas without BCL6-translocations. In contrast, t(14;18)-negative lymphomas with BCL6-translocations were amongst others of higher grade, less often CD10-positive, involved the bone marrow less frequently and did not infiltrate the lymph node capsule. BCL2- and BCL6-translocations correlate with particular phenotypes of follicular lymphomas. ...
Determinants of the t(14;18) translocation and their role in t(14;18)-positive follicular lymphoma
Cancer Causes & Control, 2015
Purpose The strong association between t(14;18) translocation and follicular lymphoma (FL) is well known. However, the determinants of this chromosomal aberration and their role in t(14;18) associated FL remain to be established. Methods t(14;18) frequency within the B cell lymphoma 2 major breakpoint region was determined for 135 incident FL cases and 251 healthy controls as part of a nested casecontrol study within the European Prospective Investigation into Cancer cohort. Quantitative real-time PCR was performed in DNA extracted from blood samples taken at recruitment. The relationship between prevalence and frequency of the translocation with baseline anthropometric, lifestyle, and dietary factors in cases and controls was determined. Unconditional logistic regression was used to explore whether the risk of FL associated with these factors differed in t(14;18) ? as compared to t(14;18)cases.
Blood, 2009
Follicular lymphoma (FL) is genetically characterized by the presence of the t(14;18)(q32; q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14;18), their t(14;18)-negative counterparts are less well studied about their immunohistochemical, genetic, molecular, and clinical features. Within a previously published series of 184 FLs grades 1 to 3A with available gene expression data, we identified 17 FLs lacking the t(14;18). Comparative genomic hybridization and high-resolution single nucleotide polymorphism (SNP) array profiling showed that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14;18)-positive FL subgroup. A comparison of gene expression profiles showed an enrichment of germinal center B cell-associated signatures in t(14;18)-positive FL, whereas activated B cell-like, NFB, proliferation, and bystander cell signatures were enriched in t(14;18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FLs, in which 32% of t(14;18)-negative FLs showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14;18), our findings suggest distinct molecular features of t
Detection of t(14;18) in Turkish follicular lymphomas using the polymerase chain reaction
Leukemia Research, 2000
A t(14;18) translocation is closely associated with the follicular lymphoma but is also seen in diffuse B cell lymphomas with a previous history of a follicular lymphoma as well as de novo diffuse lymphomas. Estimation of the frequency of t(14;18) in follicular lymphoma vary widely from 33 to 89%. Furthermore, no extensive data have been published on the frequency of t(14;18) in Turkish cases of follicular lymphoma. Representative tissue blocks from 67 patients with follicular lymphoma, 12 cases of diffuse large B cell lymphomas and 11 cases of reactive hyperplasias were examined for the presence of this translocation using PCR. DNA probes capable of detecting rearrangement at both the major and minor break point regions were employed. We could detect t(14;18) in 46 out of 67 cases (68.7%) of follicular and 25% of diffuse large B cell lymphomas. In follicular lymphomas 64.2% of these break points were at mbr and 4.5% were at the mcr region. Review of the literature showed that comparable results have been obtained previously using molecular techniques. Our data showed that despite the relative infrequency of follicular lymphomas in the Turkish population these lymphomas share a common molecular pathogenesis with involvement of bcl-2 gene and background incidence of such rearrangement is similar in all populations, regardless the incidence of folicular lymphoma.
Leukemia, 2002
Translocations involving the BCL-6 gene are frequently observed in diffuse large B cell lymphoma, but have rarely been reported in follicular lymphoma (FL). We studied a distinct cohort of FLs with a 3q27/BCL-6 gene rearrangement, but lacking the t(14;18) translocation. In 13/15 cases, translocations involved the 3q27 and the 14q32 regions. All cases displayed a marked follicular growth pattern and, in some instances, a monocytoid component. Tumor cells were CD5 − CD20 + CD23 − CD43 − BCL-6 + , and in the main CD10 negative (n = 10, 71%) and BCL-2 negative (n = 11, 78%). When compared to 20 typical t(14;18) + FLs, the presence of large follicles (P = 0.01) and a CD10 − /BCL-2 − phenotype were more frequently observed (P = 0.001) in our cohort. Clonal mutations arising in the BCL-6 first intron were observed in 5/7 cases with evidence of intraclonal heterogeneity, consistent with a germinal center origin. No significant difference was found in comparison to t(14;18) + FL regarding age, sex, performance status, bone marrow involvement or overall survival. However, in the 3q27 + FL group, a stage III/IV disease and a bulky mass were less frequently observed. This study indicates that 3q27 + FL without t(14;18) translocation have peculiar clinico-pathologic features and may correspond to a rare and distinct subtype of lymphoma originating from the germinal center.
Follicular lymphoma lacking the t(14;18)(q32;q21): identification of two disease subtypes
British journal of haematology, 2003
The clinical and pathological features, including karyotype data and BCL2 protein expression pattern, of follicular lymphoma without a t(14;18)(q32;q21) have not been well defined. We have identified and conducted a detailed analysis of 50 cases with follicular lymphoma who lack the t(14;18). Fluorescent in situ hybridization (FISH) analysis was used to exclude cases with a cryptic IGH/BCL2 rearrangement. BCL2 protein expression level was assessed by immunohistochemistry. The karyotypes were assessed for recurrent sites of structural rearrangement, duplications and deletions on a band-by-band basis, and compared with a large cohort of cases with t(14;18). A distinct pattern of chromosomal alterations was identified in the cases without t(14;18). BCL2 protein overexpression was detected in 33% of 49 tested cases. In this minority, the karyotypes frequently showed increased copies of chromosome 18. The majority of cases (67%) did not show BCL2 overexpression and were characterized prominently by the presence of t(3;14)(q27;q32), implying a role for BCL6. Follicular lymphomas that lack a t(14;18) were segregated into two subgroups with distinct cytogenetic, phenotypic and possibly clinical features: one with BCL2 protein overexpression not related to an IGH/BCL2 rearrangement and a second without BCL2 overexpression. Objective identification of BCL2 expression level as well as BCL2 and BCL6 status by cytogenetic or FISH analysis has potential clinical utility and may yield insights into alternative genetic mechanisms associated with B-cell lymphomas with a follicular growth pattern.
Blood, 1992
The presence of the translocation t(8;14)(q24;q32) has not been well described in follicular lymphoma (FL). In a consecutive series of 278 karyotypically abnormal non-Hodgkin's lymphomas (NHL), six patients with FL showing a t(8;14) without a t(14;18)(q32;q21) were identified. They ranged in age from 45 to 73 years. The cell type was mixed in four patients, small-cleaved in one, and large-cleaved in one; four cases also contained diffuse areas. All cases tested displayed monoclonal surface Ig. The clinical courses were consistent with the histologic subtypes, being less aggressive than other t(8;14)-bearing NHL. In five cases, frozen tissue was available for Southern blotting. The BCL2 gene showed a germline configuration when studied with the MBR, MCR, and 5′ cDNA probes. The MYC gene also appeared unrearranged using an exon-1 probe with EcoRI or HindIII digestion. Analysis of the Ig heavy chain (IgH) gene with a JH region probe and BamHI or EcoRI digestion showed only one rear...