BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma.
Journal Article (Journal Article)
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.
- Iqbal, J; Sanger, WG; Horsman, DE; Rosenwald, A; Pickering, DL; Dave, B; Dave, S; Xiao, L; Cao, K; Zhu, Q; Sherman, S; Hans, CP; Weisenburger, DD; Greiner, TC; Gascoyne, RD; Ott, G; Müller-Hermelink, HK; Delabie, J; Braziel, RM; Jaffe, ES; Campo, E; Lynch, JC; Connors, JM; Vose, JM; Armitage, JO; Grogan, TM; Staudt, LM; Chan, WC
- July 1, 2004
Volume / Issue
- 165 / 1
Start / End Page
- 159 - 166
Pubmed Central ID
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)
- United States