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 J Dave, Sandeep Dave, Li Xiao, Kajia Cao, Qiuming Zhu, Simon Sherman, Christine P. Hans, Dennis D. Weisenburger, Timothy Charles 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 Marie Vose, James Olen Armitage, Thomas M. Grogan, Louis M. Staudt, Wing C. Chan

Research output: Contribution to journalArticle

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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

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Germinal Center
Lymphoma, Large B-Cell, Diffuse
B-Lymphocytes
Neoplasms
Fluorescence In Situ Hybridization
cdc Genes
Gene Expression Profiling
B-Cell Lymphoma
Gene Expression
Polymerase Chain Reaction
Genes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma. / Iqbal, Javeed; Sanger, Warren G.; Horsman, Douglas E.; Rosenwald, Andreas; Pickering, Diane L.; Dave, Bhavana J; Dave, Sandeep; Xiao, Li; Cao, Kajia; Zhu, Qiuming; Sherman, Simon; Hans, Christine P.; Weisenburger, Dennis D.; Greiner, Timothy Charles; Gascoyne, Randy D.; Ott, German; Müller-Hermelink, H. Konrad; Delabie, Jan; Braziel, Rita M.; Jaffe, Elaine S.; Campo, Elias; Lynch, James C.; Connors, Joseph M.; Vose, Julie Marie; Armitage, James Olen; Grogan, Thomas M.; Staudt, Louis M.; Chan, Wing C.

In: American Journal of Pathology, Vol. 165, No. 1, 07.2004, p. 159-166.

Research output: Contribution to journalArticle

Iqbal, J, Sanger, WG, Horsman, DE, Rosenwald, A, Pickering, DL, Dave, BJ, 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 2004, 'BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma', American Journal of Pathology, vol. 165, no. 1, pp. 159-166. https://doi.org/10.1016/S0002-9440(10)63284-1
Iqbal, Javeed ; Sanger, Warren G. ; Horsman, Douglas E. ; Rosenwald, Andreas ; Pickering, Diane L. ; Dave, Bhavana J ; Dave, Sandeep ; Xiao, Li ; Cao, Kajia ; Zhu, Qiuming ; Sherman, Simon ; Hans, Christine P. ; Weisenburger, Dennis D. ; Greiner, Timothy Charles ; Gascoyne, Randy D. ; Ott, German ; Müller-Hermelink, H. Konrad ; Delabie, Jan ; Braziel, Rita M. ; Jaffe, Elaine S. ; Campo, Elias ; Lynch, James C. ; Connors, Joseph M. ; Vose, Julie Marie ; Armitage, James Olen ; Grogan, Thomas M. ; Staudt, Louis M. ; Chan, Wing C. / BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma. In: American Journal of Pathology. 2004 ; Vol. 165, No. 1. pp. 159-166.
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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.",
author = "Javeed Iqbal and Sanger, {Warren G.} and Horsman, {Douglas E.} and Andreas Rosenwald and Pickering, {Diane L.} and Dave, {Bhavana J} and Sandeep Dave and Li Xiao and Kajia Cao and Qiuming Zhu and Simon Sherman and Hans, {Christine P.} and Weisenburger, {Dennis D.} and Greiner, {Timothy Charles} and Gascoyne, {Randy D.} and German Ott and M{\"u}ller-Hermelink, {H. Konrad} and Jan Delabie and Braziel, {Rita M.} and Jaffe, {Elaine S.} and Elias Campo and Lynch, {James C.} and Connors, {Joseph M.} and Vose, {Julie Marie} and Armitage, {James Olen} and Grogan, {Thomas M.} and Staudt, {Louis M.} and Chan, {Wing C.}",
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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 J

AU - Dave, Sandeep

AU - Xiao, Li

AU - Cao, Kajia

AU - Zhu, Qiuming

AU - Sherman, Simon

AU - Hans, Christine P.

AU - Weisenburger, Dennis D.

AU - Greiner, Timothy Charles

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 Marie

AU - Armitage, James Olen

AU - Grogan, Thomas M.

AU - Staudt, Louis M.

AU - Chan, Wing C.

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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