The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile

Author:

Huang James Z.1,Sanger Warren G.1,Greiner Timothy C.1,Staudt Louis M.1,Weisenburger Dennis D.1,Pickering Diane L.1,Lynch James C.1,Armitage James O.1,Warnke Roger A.1,Alizadeh Ash A.1,Lossos Izidore S.1,Levy Ronald1,Chan Wing C.1

Affiliation:

1. From the Departments of Pathology and Microbiology, The Munroe-Meyer Institute for Genetics and Rehabilitation, Preventive and Social Medicine and Internal Medicine, University of Nebraska Medical Center, Omaha; Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD; and Departments of Pathology, Biochemistry, and Medicine, Stanford University Medical Center, Stanford, CA.

Abstract

Recently we have identified subgroups of de novo primary diffuse large B-cell lymphoma (DLBCL) based on complementary DNA microarray-generated gene expression profiles. To correlate the gene expression profiles with cytogenetic abnormalities in these DLBCLs, we examined the occurrence of the t(14;18)(q32;q21) in the 2 distinctive subgroups of DLBCL: one with the germinal center B-cell gene expression signature and the other with the activated B cell–like gene expression signature. The t(14;18) was detected in 7 of 35 cases (20%). All 7 t(14;18)-positive cases had a germinal center B-cell gene expression profile, representing 35% of the cases in this subgroup, and 6 of these 7 cases had very similar gene expression profiles. The expression of bcl-2 and bcl-6 proteins was not significantly different between the t(14;18)-positive and -negative cases, whereas CD10 was detected only in the group with the germinal center B-cell expression profile, and CD10 was most frequently expressed in the t(14;18)-positive cases. This study supports the validity of subdividing DLBCL into 2 major subgroups by gene expression profiling, with the t(14;18) being an important event in the pathogenesis of a subset of DLBCL arising from germinal center B cells. CD10 protein expression is useful in identifying cases of DLBCL with a germinal center B-cell gene expression profile and is often expressed in cases with the t(14;18).

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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