title: BCL2 translocation defines a unique tumor subset within the germinal center B-cell-like diffuse large B-cell lymphoma.
abstract: 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.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, 983135 Nebraska Medical Center, Omaha, NE 68198-3135, USA.
authors.forename: Javeed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Warren G
authors.initials: WG
authors.lastname: Sanger
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Horsman
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Diane L
authors.initials: DL
authors.lastname: Pickering
authors.forename: Bhavana
authors.initials: B
authors.lastname: Dave
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dave
authors.forename: Li
authors.initials: L
authors.lastname: Xiao
authors.forename: Kajia
authors.initials: K
authors.lastname: Cao
authors.forename: Quiming
authors.initials: Q
authors.lastname: Zhu
authors.forename: Simon
authors.initials: S
authors.lastname: Sherman
authors.forename: Christine P
authors.initials: CP
authors.lastname: Hans
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: H Konrad
authors.initials: HK
authors.lastname: Müller-Hermelink
authors.forename: Jan
authors.initials: J
authors.lastname: Delabie
authors.forename: Rita M
authors.initials: RM
authors.lastname: Braziel
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: James C
authors.initials: JC
authors.lastname: Lynch
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: James O
authors.initials: JO
authors.lastname: Armitage
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Grogan
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
mesh_terms: 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
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C090468:TP53BP2 protein, human; D019938:Cyclin D1; D015260:Neprilysin