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Heterogeneous Breakpoints on the Immunoglobulin Genes Are Involved in Fusion with the 5′ Region of BCL2 in B‐Cell Tumors
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 he...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2001
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926849/ https://www.ncbi.nlm.nih.gov/pubmed/11572760 http://dx.doi.org/10.1111/j.1349-7006.2001.tb01183.x |
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author | Yonetani, Noboru Ueda, Chiyoko Akasaka, Takashi Nishikori, Momoko Uchiyama, Takashi Ohno, Hitoshi |
author_facet | Yonetani, Noboru Ueda, Chiyoko Akasaka, Takashi Nishikori, Momoko Uchiyama, Takashi Ohno, Hitoshi |
author_sort | Yonetani, Noboru |
collection | PubMed |
description | 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/IGLK 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 K‐deleting element, which is located 24 kb downstream of the constant region of IGLK, followed the 5′‐BCL2 in another case. One 5′‐BCL2/IGLK and two 5′‐BCL2/IGLλ junctions involved intronic regions where the normal recombination process does not occur. In the remaining one case, the 5′‐BCL2 fused 3’of a Vλ, gene that was upstream of another Vλ/Jλ 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). |
format | Online Article Text |
id | pubmed-5926849 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59268492018-05-11 Heterogeneous Breakpoints on the Immunoglobulin Genes Are Involved in Fusion with the 5′ Region of BCL2 in B‐Cell Tumors Yonetani, Noboru Ueda, Chiyoko Akasaka, Takashi Nishikori, Momoko Uchiyama, Takashi Ohno, Hitoshi Jpn J Cancer Res Article 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/IGLK 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 K‐deleting element, which is located 24 kb downstream of the constant region of IGLK, followed the 5′‐BCL2 in another case. One 5′‐BCL2/IGLK and two 5′‐BCL2/IGLλ junctions involved intronic regions where the normal recombination process does not occur. In the remaining one case, the 5′‐BCL2 fused 3’of a Vλ, gene that was upstream of another Vλ/Jλ 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). Blackwell Publishing Ltd 2001-09 /pmc/articles/PMC5926849/ /pubmed/11572760 http://dx.doi.org/10.1111/j.1349-7006.2001.tb01183.x Text en |
spellingShingle | Article Yonetani, Noboru Ueda, Chiyoko Akasaka, Takashi Nishikori, Momoko Uchiyama, Takashi Ohno, Hitoshi Heterogeneous Breakpoints on the Immunoglobulin Genes Are Involved in Fusion with the 5′ Region of BCL2 in B‐Cell Tumors |
title | Heterogeneous Breakpoints on the Immunoglobulin Genes Are Involved in Fusion with the 5′ Region of BCL2 in B‐Cell Tumors |
title_full | Heterogeneous Breakpoints on the Immunoglobulin Genes Are Involved in Fusion with the 5′ Region of BCL2 in B‐Cell Tumors |
title_fullStr | Heterogeneous Breakpoints on the Immunoglobulin Genes Are Involved in Fusion with the 5′ Region of BCL2 in B‐Cell Tumors |
title_full_unstemmed | Heterogeneous Breakpoints on the Immunoglobulin Genes Are Involved in Fusion with the 5′ Region of BCL2 in B‐Cell Tumors |
title_short | Heterogeneous Breakpoints on the Immunoglobulin Genes Are Involved in Fusion with the 5′ Region of BCL2 in B‐Cell Tumors |
title_sort | heterogeneous breakpoints on the immunoglobulin genes are involved in fusion with the 5′ region of bcl2 in b‐cell tumors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926849/ https://www.ncbi.nlm.nih.gov/pubmed/11572760 http://dx.doi.org/10.1111/j.1349-7006.2001.tb01183.x |
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