Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell–like diffuse large B cell lymphoma

To elucidate the mechanisms underlying chromosomal translocations in diffuse large B cell lymphoma (DLBCL), we investigated the nature and extent of immunoglobulin class switch recombination (CSR) in these tumors. We used Southern blotting to detect legitimate and illegitimate CSR events in tumor sa...

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Main Authors:	Lenz, Georg, Nagel, Inga, Siebert, Reiner, Roschke, Anna V., Sanger, Warren, Wright, George W., Dave, Sandeep S., Tan, Bruce, Zhao, Hong, Rosenwald, Andreas, Muller-Hermelink, Hans Konrad, Gascoyne, Randy D., Campo, Elias, Jaffe, Elaine S., Smeland, Erlend B., Fisher, Richard I., Kuehl, W. Michael, Chan, Wing C., Staudt, Louis M.
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2007
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2137913/

id	pubmed-2137913
recordtype	oai_dc
spelling	pubmed-21379132007-12-13 Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell–like diffuse large B cell lymphoma Lenz, Georg Nagel, Inga Siebert, Reiner Roschke, Anna V. Sanger, Warren Wright, George W. Dave, Sandeep S. Tan, Bruce Zhao, Hong Rosenwald, Andreas Muller-Hermelink, Hans Konrad Gascoyne, Randy D. Campo, Elias Jaffe, Elaine S. Smeland, Erlend B. Fisher, Richard I. Kuehl, W. Michael Chan, Wing C. Staudt, Louis M. Articles To elucidate the mechanisms underlying chromosomal translocations in diffuse large B cell lymphoma (DLBCL), we investigated the nature and extent of immunoglobulin class switch recombination (CSR) in these tumors. We used Southern blotting to detect legitimate and illegitimate CSR events in tumor samples of the activated B cell–like (ABC), germinal center B cell–like (GCB), and primary mediastinal B cell lymphoma (PMBL) subgroups of DLBCL. The frequency of legitimate CSR was lower in ABC DLBCL than in GCB DLBCL and PMBL. In contrast, ABC DLBCL had a higher frequency of internal deletions within the switch μ (Sμ) region compared with GCB DLBCL and PMBL. ABC DLBCLs also had frequent deletions within Sγ and other illegitimate switch recombinations. Sequence analysis revealed ongoing Sμ deletions within ABC DLBCL tumor clones, which were accompanied by ongoing duplications and activation-induced cytidine deaminase–dependent somatic mutations. Unexpectedly, short fragments derived from multiple chromosomes were interspersed within Sμ in one case. These findings suggest that ABC DLBCLs have abnormalities in the regulation of CSR that could predispose to chromosomal translocations. Accordingly, aberrant switch recombination was responsible for translocations in ABC DLBCLs involving BCL6, MYC, and a novel translocation partner, SPIB. The Rockefeller University Press 2007-03-19 /pmc/articles/PMC2137913/ /pubmed/17353367 http://dx.doi.org/10.1084/jem.20062041 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Lenz, Georg Nagel, Inga Siebert, Reiner Roschke, Anna V. Sanger, Warren Wright, George W. Dave, Sandeep S. Tan, Bruce Zhao, Hong Rosenwald, Andreas Muller-Hermelink, Hans Konrad Gascoyne, Randy D. Campo, Elias Jaffe, Elaine S. Smeland, Erlend B. Fisher, Richard I. Kuehl, W. Michael Chan, Wing C. Staudt, Louis M.
spellingShingle	Lenz, Georg Nagel, Inga Siebert, Reiner Roschke, Anna V. Sanger, Warren Wright, George W. Dave, Sandeep S. Tan, Bruce Zhao, Hong Rosenwald, Andreas Muller-Hermelink, Hans Konrad Gascoyne, Randy D. Campo, Elias Jaffe, Elaine S. Smeland, Erlend B. Fisher, Richard I. Kuehl, W. Michael Chan, Wing C. Staudt, Louis M. Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell–like diffuse large B cell lymphoma
author_facet	Lenz, Georg Nagel, Inga Siebert, Reiner Roschke, Anna V. Sanger, Warren Wright, George W. Dave, Sandeep S. Tan, Bruce Zhao, Hong Rosenwald, Andreas Muller-Hermelink, Hans Konrad Gascoyne, Randy D. Campo, Elias Jaffe, Elaine S. Smeland, Erlend B. Fisher, Richard I. Kuehl, W. Michael Chan, Wing C. Staudt, Louis M.
author_sort	Lenz, Georg
title	Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell–like diffuse large B cell lymphoma
title_short	Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell–like diffuse large B cell lymphoma
title_full	Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell–like diffuse large B cell lymphoma
title_fullStr	Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell–like diffuse large B cell lymphoma
title_full_unstemmed	Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell–like diffuse large B cell lymphoma
title_sort	aberrant immunoglobulin class switch recombination and switch translocations in activated b cell–like diffuse large b cell lymphoma
description	To elucidate the mechanisms underlying chromosomal translocations in diffuse large B cell lymphoma (DLBCL), we investigated the nature and extent of immunoglobulin class switch recombination (CSR) in these tumors. We used Southern blotting to detect legitimate and illegitimate CSR events in tumor samples of the activated B cell–like (ABC), germinal center B cell–like (GCB), and primary mediastinal B cell lymphoma (PMBL) subgroups of DLBCL. The frequency of legitimate CSR was lower in ABC DLBCL than in GCB DLBCL and PMBL. In contrast, ABC DLBCL had a higher frequency of internal deletions within the switch μ (Sμ) region compared with GCB DLBCL and PMBL. ABC DLBCLs also had frequent deletions within Sγ and other illegitimate switch recombinations. Sequence analysis revealed ongoing Sμ deletions within ABC DLBCL tumor clones, which were accompanied by ongoing duplications and activation-induced cytidine deaminase–dependent somatic mutations. Unexpectedly, short fragments derived from multiple chromosomes were interspersed within Sμ in one case. These findings suggest that ABC DLBCLs have abnormalities in the regulation of CSR that could predispose to chromosomal translocations. Accordingly, aberrant switch recombination was responsible for translocations in ABC DLBCLs involving BCL6, MYC, and a novel translocation partner, SPIB.
publisher	The Rockefeller University Press
publishDate	2007
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2137913/
_version_	1611420845267222528

Aberrant immunoglobulin class switch recombination and switch translocations in activated B cell–like diffuse large B cell lymphoma

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