Major and minor breakpoint sites of chromosomal translocation t(14;18) in subtypes of non-Hodgkin's lymphomas (original) (raw)
Related papers
Cancer research, 1991
We have examined 165 unselected cases of non-Hodgkin's lymphomas for rearrangements involving the t(14;18) major breakpoint region using a polymerase chain reaction (PCR) and direct sequencing of amplified major breakpoint region bcl-2/JH junctional regions. The lymphomas, diagnosed according to the updated Kiel classification, consisted of 33 centroblastic-centrocytic, 37 centroblastic, 27 immunocytic, 10 immunoblastic, 10 centrocytic, 2 lymphoblastic, 2 Ki-1-positive anaplastic large cell, 14 peripheral T-cell, and 4 unclassified lymphomas. In addition 18 chronic lymphocytic leukemias, 2 hairy cell leukemias, and 6 plasmacytomas were studied. In 17 cases a bcl-2/JH gene fusion sequence was amplified by PCR. A bcl-2/JH gene fusion was detected only in three lymphoma subgroups: 13 of 33 centroblastic-centrocytic (39%), 2 of 37 centroblastic (6%), and 2 of 27 immunocytic (8%) were positive. In two cases, major breakpoint region bcl-2 rearrangements verified by genomic Southern an...
Refinement of lymphoma cytogenetics by the chromosome 18q21 major breakpoint region
Blood, 1987
A small (2.8-kilobase, kb) major breakpoint region localized to segment 18q21 rearranges in greater than 70% of t(14;18)(q32;q21) lymphomas. This rearrangement interrupts the Bcl-2 gene and introduces it into the Ig locus at 14q32. The rearrangement between the joining region (JH) of Ig on chromosome 14 and the 18q21 region creates a translocation-specific DNA rearrangement. We generated probes that distinguish the 14;18 juncture on the derivative (der) 14 and der (18) chromosomes, providing a molecular approach to t(14;18) identification. Approximately 60% of unselected follicular lymphomas, 20% of diffuse large cell lymphomas, and 50% of adult undifferentiated non-Burkitt lymphomas demonstrated 14;18 rearrangements within the major breakpoint region. Examination of DNA for 14;18 rearrangements resolved the identity of 14q+ chromosomes in two patient's cells that lacked an obvious reciprocal partner. Identification of the exact restriction fragments that mediate translocations ...
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, 2008
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 pred...
Alternative end-joining in follicular lymphomas’ t(14;18) translocation
Leukemia, 2002
T(14;18) chromosomal translocation is assumed to result from illegitimate rearrangement between the BCL2 proto-oncogene and the IGH locus during the D H to J H joining phase of V(D)J recombination in early B cells. Analysis of the breakpoint junctions suggests that translocation derives from the fusion between normal V(D)J recombination intermediates at the IGH locus and non-V(D)J-mediated broken-ends at the BCL2 locus. So far, BCL2 broken-ends have only been observed fused to coding-ends, raising questions concerning the molecular constraints of the illegitimate joining process. Using a combination of genome walking and long-range PCR assays, we describe in this report that in 4.5% 2/44) of the t(14;18), one of the BCL2 broken-ends is fused to a signal-end. The formation of these J H RSS/BCL2 junctions provides direct evidence that BCL2 broken-ends are capable of joining to both products of V(D)J recombination, suggesting their presence in the RAG-mediated post-cleavage complex. In addition, junctions generated by this alternative end-joining do not involve deletion of the chromosome 14 intervening sequences generally lost in the standard translocation, providing a unique opportunity to investigate the rearrangement status of this region in the translocated IGH allele. In both cases, a DJ H rearrangement could be detected 5Ј of the J H -RSS/BCL2 junction. These findings, together with the previously reported bias towards the most external D H and J H segments in standard breakpoints, strongly suggest that t(14;18) preferentially occurs during an attempted secondary D H to J H rearrangement. This unusual and restricted window of differentiation opens intriguing questions concerning the etiology of the translocation. Leukemia (2002) 16, 120-126. Novel t(14;18) junctions in follicular lymphoma R Marculescu et al 124 Leukemia Novel t(14;18) junctions in follicular lymphoma R Marculescu et al 125
Science, 1984
The breakpoint of t(ll;l-4)(q23;q32) chromosome translocation in a B-cell lymphoma line, RC-K8, »ascloned. Immunoglobulin heavy chain (ICH) constant gene, C^2 at the 5' end, was involved in this transloca tion, and the DNA segment juxtaposed to the Oy2 was proved to be derived from chromosome 11 by somatic cell hybrid study. The normal counterpart of chromosome 11 was also isolated. With a DNA probe near the breakpoint of chromosome 11, Southern blot analysis of RC-K8 and 10 other cases with translocation involving the Ilq23 region was conducted, but no rearrangement bands have been observed thus far except for RC-K8.
Modern Pathology, 2009
A frequent chromosomal translocation in mature B-cell non-Hodgkin lymphoma affects band 3q27 and results in deregulation of the B-cell lymphoma 6 (BCL6) gene. Two breakpoint clusters have been described thus far, the major breakpoint region (MBR) and an alternative breakpoint region (ABR) that is located 245-285 kb 5' to BCL6. Translocation at the MBR predominates in diffuse large B-cell lymphoma, whereas translocation at the ABR is reported to be frequently associated with grade 3B follicular lymphoma. However, translocation at the ABR has not been studied in a large series of follicular lymphomas, particularly t(14;18)-negative follicular lymphomas. Therefore, we studied BLC6 rearrangements at the MBR and ABR by using breakapart fluorescence in situ hybridization (FISH) probes in 142 cases of follicular lymphomas, including 63 t(14;18)-negative and 79 t(14;18)-positive cases. Conventional cytogenetic (karyotype) analysis was also performed in 58 of the 63 t(14;18)-negative cases. BCL6 rearrangement was found in 26% of t(14;18)-negative and 19% of t(14;18)-positive follicular lymphoma. t(14;18)-negative cases showed a high frequency of rearrangement at the ABR (12%) with an ABR:MBR ratio of 0.86, compared to only 5% with an ABR:MBR ratio of 0.36 in the t(14;18)-positive cases. BCL6 rearrangements were found in all grades of follicular lymphoma but were most frequent in grade 3 t(14;18)-negative follicular lymphoma (60%). FISH analysis had a higher sensitivity for detecting BCL6 rearrangements than conventional cytogenetics. In conclusion, BCL6 rearrangements occur at a similar frequency in t(14;18)-negative follicular lymphoma and diffuse large B-cell lymphoma. However, t(14;18)-negative follicular lymphoma appears to have a higher frequency of rearrangement at the ABR compared with t(14;18)-positive follicular lymphoma and diffuse large B-cell lymphoma. Therefore, it is important to perform Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
Annals of Hematology, 1991
Three patients with centrocytic/centroblastic lymphoma developed a rapidly fatal leukemic transformation of the disease after a transient remission. At the time of transformation, cytogenetic analysis revealed in all patients abnormal karyotypes with coexistence of t (14; 18) and t (8; 22). Molecular analysis in one patient showed rearrangement of the BCL2 oncogene and c-myc m-RNA expression. These findings imply that translocation t (14; 18) was present during the first phase of the disease and that acquisition of translocation t (8; 22) was accompanied by leukemic transformation.
The pattern and frequency of t(14;18) translocation and immunophenotype in Asian follicular lymphoma
Aims: Follicular lymphoma is frequently associated with t(14;18)(q32;q21) translocation. This study was undertaken to determine the pattern of Bcl-2, CD10 and Bcl-6 expression in relation to t(14;18) translocation in follicular lymphoma from a cohort of a multi-ethnic Asian population. Methods and results: Sixty-two cases of follicular lymphoma were retrieved for immunohistochemistry, and t(14;18) translocation analysis by polymerase chain reaction and fluorescent in-situ hybridization techniques. Bcl-2 expression was present in 74% of the cases. CD10 expression was also relatively low (61%), with decreasing frequency of expression in high-grade tumours. Bcl-6 protein was expressed in most of the tumours (88%) regardless of the tumour grade. The t(14;18) translocation was detected in 46 cases (74%) with an extremely high rate of t(14;18) translocation in ethnic Indian cases (100%). Conclusion: The frequency of t(14;18) translocation in this series of follicular lymphomas was higher ...