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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...

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Autores principales: Yonetani, Noboru, Ueda, Chiyoko, Akasaka, Takashi, Nishikori, Momoko, Uchiyama, Takashi, Ohno, Hitoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2001
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).
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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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