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Cancer Cell. 2010 Dec 14;18(6):568-79. doi: 10.1016/j.ccr.2010.10.030.

BLIMP1 is a tumor suppressor gene frequently disrupted in activated B cell-like diffuse large B cell lymphoma.

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  • 1Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.

Abstract

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease composed of at least two distinct subtypes: germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL. These phenotypic subtypes segregate with largely unique genetic lesions, suggesting the involvement of different pathogenetic mechanisms. In this report we show that the BLIMP1/PRDM1 gene is inactivated by multiple mechanisms, including homozygous deletions, truncating or missense mutations, and transcriptional repression by constitutively active BCL6, in ∼53% of ABC-DLBCL. In vivo, conditional deletion of Blimp1 in mouse B cells promotes the development of lymphoproliferative disorders recapitulating critical features of the human ABC-DLBCL. These results demonstrate that BLIMP1 is a bona fide tumor-suppressor gene whose loss contributes to lymphomagenesis by blocking plasma cell differentiation.

Copyright © 2010 Elsevier Inc. All rights reserved.

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PMID:
21156281
[PubMed - indexed for MEDLINE]
PMCID:
PMC3030476
Free PMC Article

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