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10.1111/j.1349-7006.2001.tb01183.x

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suck abstract from ncbi


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pmid11572760
      Jpn+J+Cancer+Res 2001 ; 92 (9 ): 933-40
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  • Heterogeneous breakpoints on the immunoglobulin genes are involved in fusion with the 5 region of BCL2 in B-cell tumors #MMPMID11572760
  • Yonetani N ; Ueda C ; Akasaka T ; Nishikori M ; Uchiyama T ; Ohno H
  • Jpn J Cancer Res 2001[Sep]; 92 (9 ): 933-40 PMID11572760 show ga
  • The 5' flanking region of the BCL2 gene (5'-BCL2) is a breakpoint cluster of rearrangements with immunoglobulin genes (IGs). In contrast to t(14;18)(q32;q21) affecting the 3' region of BCL2, 5'-BCL2 can fuse to not only the heavy chain gene (IGH), but also two light chain gene (IGL) loci. We report here cloning and sequencing of a total of eleven 5'-BCL2 / IGs junctional areas of B-cell tumors, which were amplified by long-distance polymerase chain reaction-based assays. The breakpoints on 5'-BCL2 were distributed from 378 to 2312 bp upstream of the translational initiation site and, reflecting the alteration of regulatory sequences of BCL2, 5'-BCL2 / IGs-positive cells showed markedly higher levels of BCL2 expression than those of t(14;18)-positive cells. In contrast, the breakpoints on the IGs were variable. Two 5'-BCL2 / IGH and two 5'-BCL2 / IGLkappa junctions occurred 5' of the joining (J) segments, suggesting operation of an erroneous variable (V) / diversity (D) / J and V / J rearrangement mechanism. However, two other 5'-BCL2 / IGH junctions affected switch regions, and the kappa-deleting element, which is located 24 kb downstream of the constant region of IGLkappa, followed the 5'-BCL2 in another case. One 5'-BCL2 / IGLkappa and two 5'-BCL2 / IGLlambda junctions involved intronic regions where the normal recombination process does not occur. In the remaining one case, the 5'-BCL2 fused 3' of a Vlambda gene that was upstream of another Vlambda / Jlambda complex carrying a non-producing configuration, indicating that the receptor editing mechanism was likely involved in this rearrangement. Our study revealed heterogeneous anatomy of the 5'-BCL2 / IGs fusion gene leading to transcriptional activation of BCL2, and suggested that the mechanisms underlying the formation of this particular oncogene / IGs recombination are not identical to those of t(14;18).
  • |*Chromosome Breakage [MESH]
  • |*Genes, Immunoglobulin [MESH]
  • |*Genes, bcl-2 [MESH]
  • |Base Sequence [MESH]
  • |Chromosomes, Human, Pair 14/*genetics/ultrastructure [MESH]
  • |Chromosomes, Human, Pair 18/*genetics/ultrastructure [MESH]
  • |DNA Nucleotidyltransferases/metabolism [MESH]
  • |Exons/genetics [MESH]
  • |Gene Expression Regulation, Neoplastic [MESH]
  • |Humans [MESH]
  • |Immunoglobulin Heavy Chains/genetics [MESH]
  • |Immunoglobulin Variable Region/genetics [MESH]
  • |Immunoglobulin kappa-Chains/genetics [MESH]
  • |Immunoglobulin lambda-Chains/genetics [MESH]
  • |Introns/genetics [MESH]
  • |Leukemia, Lymphocytic, Chronic, B-Cell/*genetics [MESH]
  • |Lymphoma, B-Cell/*genetics [MESH]
  • |Lymphoma, Follicular/genetics [MESH]
  • |Lymphoma, Large B-Cell, Diffuse/genetics [MESH]
  • |Lymphoma, Large-Cell, Immunoblastic/genetics [MESH]
  • |Molecular Sequence Data [MESH]
  • |Oncogene Proteins, Fusion/*genetics [MESH]
  • |Polymerase Chain Reaction [MESH]
  • |Sequence Alignment [MESH]
  • |Sequence Homology, Nucleic Acid [MESH]
  • |Translocation, Genetic/*genetics [MESH]


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