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BCL2 Translocation Defines a Unique Tumor Subset within the Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma
The American Journal of Pathology
  • Javeed Iqbal, University of Nebraska Medical Center
  • Warren G. Sanger, University of Nebraska Medical Center
  • Andreas Rosenwald, University of Würzburg
  • Diane L. Pickering, University of Nebraska Medical Center
  • Barbara Dave, University of Nebraska Medical Center
  • Sandeep Dave
  • Li Xiao, University of Nebraska Medical Center
  • Kahai Cao, University of Nebraska at Omaha
  • Qiuming Zhu, University of Nebraska at Omaha
  • Simon Sherman, University of Nebraska Medical Center
  • Christine P. Hans, University of Nebraska Medical Center
  • Dennis D. Weisenburger, University of Nebraska Medical Center
  • Timothy C. Greiner, University of Nebraska Medical Center
  • Randy D. Gascoyne
  • German Ott, University of Würzburg
  • H. Konrad Müller-Hermelink, University of Würzburg
  • Jan Delabie
  • Rita M. Braziel
  • Elaine S. Jaffe
  • Elias Campo, University of Barcelona
  • James C. Lynch, University of Nebraska Medical Center
  • Joseph M. Conners, University of Barcelona
  • Julie M. Vose, University of Nebraska Medical Center
  • James O. Armitage, University of Nebraska Medical Center
  • Thomas M. Grogan, University of Arizona
  • Louis M. Staudt
  • Wing C. Chan, University of Nebraska Medical Center
Document Type
Article
Publication Date
7-1-2004
Disciplines
Abstract

Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed prognostically important subgroups: germinal center B-cell-like (GCB) DLBCL, activated B cell-like (ABC) DLBCL, and primary mediastinal large B-cell lymphoma. The t(14;18)(q32;q21) has been reported previously to define a unique subset within the GCB-DLBCL. We evaluated for the translocation in 141 cases of DLBCL that were successfully gene expression profiled. Using a dual-probe fluorescence in situ hybridization assay, we detected the t(14;18) in 17% of DLBCLs and in 34% of the GCB subgroup which contained the vast majority of positive cases. In addition, 12 t(14;18)-positive cases detected by polymerase chain reaction assays on additional samples were added to the fluorescence in situ hybridization-positive cases for subsequent analysis. Immunohistochemical data indicated that BCL2, BCL6, and CD10 protein were preferentially expressed in the t(14;18)-positive cases as compared to t(14;18)-negative cases. Within the GCB subgroup, the expression of BCL2 and CD10, but not BCL6, differed significantly between cases with or without the t(14;18): 88% versus 24% for BCL2 and 72% versus 32% for CD10, respectively. In the GCB-DLBCL subgroup, a heterogeneous group of genes is overexpressed in the t(14;18)-positive subset, among which BCL2 is a significant discriminator. Interestingly, the t(14;18)-negative subset is dominated by overexpression of cell cycle-associated genes, indicating that these tumors are significantly more proliferative, suggesting distinctive pathogenetic mechanisms. However, despite this higher proliferative activity, there was no significant difference in overall or failure-free survival between the t(14;18)-positive and -negative subsets within the GCB subgroup.

Comments

The final published version of this article can be found at: doi:10.1016/S0002-9440(10)63284-1.

© 2004. This manuscript version is made available under the CC-BY-NC-ND 4.0 licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/

Citation Information
Javeed Iqbal, Warren G. Sanger, Andreas Rosenwald, Diane L. Pickering, et al.. "BCL2 Translocation Defines a Unique Tumor Subset within the Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma" The American Journal of Pathology Vol. 165 Iss. 1 (2004) p. 159 - 166
Available at: http://works.bepress.com/qiuming-zhu/31/