TY - JOUR
T1 - BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma
AU - Iqbal, Javeed
AU - Sanger, Warren G.
AU - Horsman, Douglas E.
AU - Rosenwald, Andreas
AU - Pickering, Diane L.
AU - Dave, Bhavana
AU - Dave, Sandeep
AU - Xiao, Li
AU - Cao, Kajia
AU - Zhu, Quiming
AU - Sherman, Simon
AU - Hans, Christine P.
AU - Weisenburger, Dennis D.
AU - Greiner, Timothy C.
AU - Gascoyne, Randy D.
AU - Ott, German
AU - Müller-Hermelink, H. Konrad
AU - Delabie, Jan
AU - Braziel, Rita M.
AU - Jaffe, Elaine S.
AU - Campo, Elias
AU - Lynch, James C.
AU - Connors, Joseph M.
AU - Vose, Julie M.
AU - Armitage, James O.
AU - Grogan, Thomas M.
AU - Staudt, Louis M.
AU - Chan, Wing C.
N1 - Funding Information:
Supported in part by United States Public Health Service grants CA36727 and CA84967 awarded by the National Cancer Institute, Department of Health and Human Services.
PY - 2004/7
Y1 - 2004/7
N2 - 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.
AB - 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.
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U2 - 10.1016/S0002-9440(10)63284-1
DO - 10.1016/S0002-9440(10)63284-1
M3 - Article
C2 - 15215171
AN - SCOPUS:3042594986
SN - 0002-9440
VL - 165
SP - 159
EP - 166
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -