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VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
Published on: December 28, 2015
Multiple breakpoints within the BCL-1 locus in B-cell lymphoma: rearrangements of the cyclin D1 gene
C J de Boer1, S Loyson, P M Kluin
1Department of Pathology, University of Leiden, The Netherlands.
Insights
This study investigates BCL-1 rearrangements in centrocytic lymphoma (CC) and intermediately differentiated lymphocytic lymphoma (IDL). Southern blot analysis revealed rearrangements in 50% of CC/IDL cases, confirming their association with the t(11;14) translocation.
Area of Science:
- Hematology
- Oncology
- Cytogenetics
Background:
- Centrocytic lymphoma (CC) and intermediately differentiated lymphocytic lymphoma (IDL) are B-cell non-Hodgkin's lymphomas.
- These lymphomas are associated with the t(11;14)(q13;q32) chromosomal translocation.
- Previous research suggested a link between this translocation and BCL-1 gene rearrangements.
Purpose of the Study:
- To evaluate the association between BCL-1 gene rearrangements and CC/IDL.
- To determine the utility of Southern blot analysis in identifying these lymphomas.
Main Methods:
- Southern blot analysis was performed on 20 CC/IDL cases, 22 similar lymphomas, 11 chronic B-cell leukemias, and 2 myelomas.
- Various probes were used to cover the BCL-1 locus.
- Comigration analysis confirmed the t(11;14)(q13;q32) chromosomal rearrangement.
Main Results:
- Rearrangements within the BCL-1 locus were detected in 50% (10 of 20) of CC/IDL cases.
- Breakpoints varied, with some in the major translocation cluster (MTC) and others in different regions, including near the PRAD1/CCND1 gene.
- All confirmed cases exhibited the t(11;14)(q13;q32) translocation.
Conclusions:
- Southern blot analysis is a valuable tool for identifying CC/IDL.
- Multiple breakpoints exist across a large region of the BCL-1 locus, necessitating the use of multiple probes for comprehensive detection.
- The study reinforces the association between BCL-1 rearrangements and the t(11;14) translocation in CC/IDL.
Abstract:
Centrocytic lymphoma (CC) and intermediately differentiated lymphocytic lymphoma (IDL) are B-cell non-Hodgkin's lymphomas composed of lymphocytes presumably derived from follicle mantle cells. In these lymphomas, a specific chromosomal translocation, t(11;14)(q13;q32), has been described. Previous studies suggested an association between t(11;14) chromosomal translocations and BCL-1 rearrangements. To evaluate the association between BCL-1 rearrangements and CC/IDL, Southern blot analysis was performed on a panel of 20 cases of CC/IDL, 22 cases of morphologically similar non-Hodgkin's lymphomas, 11 cases of chronic B-cell leukemias, and 2 cases of myelomas. We used various probes covering a considerable proportion of the 120-kilobase BCL-1 locus, and rearrangements in 50% of CC/IDL (10 of 20) were detected. In CC, all 4 breakpoints were located at the major translocation cluster (MTC). In contrast, in IDL, rearrangements were detected in 3 different cluster regions: 2 cases in the MTC, 2 cases with a breakpoint 24 kilobases outside the MTC, and 2 additional cases with breakpoints found 3 kilobases 5' of the first exon of the PRAD1/CCND1 gene, which is located 120 kilobases outside the MTC. In addition, one leukemia showed a breakpoint 63 kilobases outside the MTC. In all cases, there was comigration of the rearranged 11q13 fragment and the immunoglobulin heavy chain-joining gene complex, indicating a t(11;14)(q13;q32) chromosomal rearrangement. Our results show that Southern blot analysis is helpful to identify CC/IDL, but multiple breakpoints are present over a large region, and therefore, many probes are necessary to cover all breakpoints.
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