Multiple breakpoints within the BCL-1 locus in B-cell lymphoma: rearrangements of the cyclin D1 gene

Cancer Res. 1993 Sep 15;53(18):4148-52.

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.

MeSH terms

  • Chromosome Mapping
  • Chromosomes, Human, Pair 11
  • Cyclin D1
  • Cyclins / genetics*
  • Gene Rearrangement*
  • Genes, Immunoglobulin
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Joining Region / genetics
  • Lymphoma, B-Cell / genetics*
  • Oncogene Proteins / genetics*
  • Oncogenes*
  • Proto-Oncogene Proteins / genetics*

Substances

  • Cyclins
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Joining Region
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • Cyclin D1