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

Published

Journal Article

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 mu (Smu) region compared with GCB DLBCL and PMBL. ABC DLBCLs also had frequent deletions within Sgamma and other illegitimate switch recombinations. Sequence analysis revealed ongoing Smu 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 Smu 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.

Full Text

Duke Authors

Cited Authors

  • Lenz, G; Nagel, I; Siebert, R; Roschke, AV; Sanger, W; Wright, GW; Dave, SS; Tan, B; Zhao, H; Rosenwald, A; Muller-Hermelink, HK; Gascoyne, RD; Campo, E; Jaffe, ES; Smeland, EB; Fisher, RI; Kuehl, WM; Chan, WC; Staudt, LM

Published Date

  • March 19, 2007

Published In

Volume / Issue

  • 204 / 3

Start / End Page

  • 633 - 643

PubMed ID

  • 17353367

Pubmed Central ID

  • 17353367

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.20062041

Language

  • eng

Conference Location

  • United States