BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma.
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
J
Department of Pathology and Microbiology, University of Nebraska Medical Center, 983135 Nebraska Medical Center, Omaha, NE 68198-3135, USA.
Sanger
Warren G
WG
Horsman
Douglas E
DE
Rosenwald
Andreas
A
Pickering
Diane L
DL
Dave
Bhavana
B
Dave
Sandeep
S
Xiao
Li
L
Cao
Kajia
K
Zhu
Quiming
Q
Sherman
Simon
S
Hans
Christine P
CP
Weisenburger
Dennis D
DD
Greiner
Timothy C
TC
Gascoyne
Randy D
RD
Ott
German
G
Müller-Hermelink
H Konrad
HK
Delabie
Jan
J
Braziel
Rita M
RM
Jaffe
Elaine S
ES
Campo
Elias
E
Lynch
James C
JC
Connors
Joseph M
JM
Vose
Julie M
JM
Armitage
James O
JO
Grogan
Thomas M
TM
Staudt
Louis M
LM
Chan
Wing C
WC
D051017:Apoptosis Regulatory Proteins; D001499:Bayes Theorem; D002352:Carrier Proteins / Q000378:metabolism; D002883:Chromosomes, Human, Pair 14; D019938:Cyclin D1 / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D019254:Genes, bcl-2; D018858:Germinal Center / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016393:Lymphoma, B-Cell / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000401:mortality; D015260:Neprilysin / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D016019:Survival Analysis; D015996:Survival Rate; D014178:Translocation, Genetic
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C090468:TP53BP2 protein, human; D019938:Cyclin D1; D015260:Neprilysin