BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma

Javeed Iqbal, Warren G. Sanger, Douglas E. Horsman, Andreas Rosenwald, Diane L. Pickering, Bhavana Dave, Sandeep Dave, Li Xiao, Kajia Cao, Quiming Zhu, Simon Sherman, Christine P. Hans, Dennis D. Weisenburger, Timothy C. Greiner, Randy D. Gascoyne, German Ott, H. Konrad Müller-Hermelink, Jan Delabie, Rita M. Braziel, Elaine S. JaffeElias Campo, James C. Lynch, Joseph M. Connors, Julie M. Vose, James O. Armitage, Thomas M. Grogan, Louis M. Staudt, Wing C. Chan

Research output: Contribution to journalArticle

217 Scopus citations

Abstract

Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed prognostically important subgroups: germinal center B-cell-like (GCB) DL-BCL, 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.

Original languageEnglish (US)
Pages (from-to)159-166
Number of pages8
JournalAmerican Journal of Pathology
Volume165
Issue number1
DOIs
StatePublished - Jul 2004

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Iqbal, J., Sanger, W. G., Horsman, D. E., Rosenwald, A., Pickering, D. L., Dave, B., Dave, S., Xiao, L., Cao, K., Zhu, Q., Sherman, S., Hans, C. P., Weisenburger, D. D., Greiner, T. C., Gascoyne, R. D., Ott, G., Müller-Hermelink, H. K., Delabie, J., Braziel, R. M., ... Chan, W. C. (2004). BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma. American Journal of Pathology, 165(1), 159-166. https://doi.org/10.1016/S0002-9440(10)63284-1