The American Journal of Pathology
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, Javeed; Sanger, Warren G.; Rosenwald, Andreas; Pickering, Diane L.; Dave, Barbara; Dave, Sandeep; Xiao, Li; Cao, Kahai; Zhu, Qiuming; Sherman, Simon; Hans, Christine P.; Weisenburger, Dennis D.; Greiner, Timothy C.; Gascoyne, Randy D.; Ott, German; Müller-Hermelink, H. Konrad; Delabie, Jan; Braziel, Rita M.; Jaffe, Elaine S.; Campo, Elias; Lynch, James C.; Conners, Joseph M.; Vose, Julie M.; Armitage, James O.; Grogan, Thomas M.; Staudt, Louis M.; and Chan, Wing C., "BCL2 Translocation Defines a Unique Tumor Subset within the Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma" (2004). Computer Science Faculty Publications. 52.