The Journal of Experimental Medicine
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Published 21 February 2006. doi:10.1084/jem.20052204
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 2, 311-317
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BRIEF DEFINITIVE REPORT

 Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma

Laura Pasqualucci1,2, Mara Compagno1,2, Jane Houldsworth3, Stefano Monti4, Adina Grunn1,2, Subhadra V. Nandula1,2, Jon C. Aster5, Vundavally V. Murty1,2, Margaret A. Shipp6, and Riccardo Dalla-Favera1,2

1 Institute for Cancer Genetics and 2 The Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032
3 Laboratory of Cancer Genetics and the Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021
4 Broad Institute, Massachusetts Institute of Technology, Cambridge, MA 02141
5 Department of Pathology, Brigham and Women's Hospital and 6 Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 12115

CORRESPONDENCE Riccardo Dalla-Favera: rd10{at}columbia.edu

PR domain containing 1 with zinc finger domain (PRDM1)/B lymphocyte–induced maturation protein 1 (BLIMP1) is a transcriptional repressor expressed in a subset of germinal center (GC) B cells and in all plasma cells, and required for terminal B cell differentiation. The BLIMP1 locus lies on chromosome 6q21-q22.1, a region frequently deleted in B cell lymphomas, suggesting that it may harbor a tumor suppressor gene. We report here that the BLIMP1 gene is inactivated by structural alterations in 24% (8 out of 34) activated B cell–like diffuse large cell lymphoma (ABC-DLBCL), but not in GC B cell–like (n = 0/37) or unclassified (n = 0/21) DLBCL. BLIMP1 alterations included gene truncations, nonsense mutations, frameshift deletions, and splice site mutations that generate aberrant transcripts encoding truncated BLIMP1 proteins. In all cases studied, both BLIMP1 alleles were inactivated by deletions or mutations. Furthermore, most non–GC type DLBCL cases (n = 20/26, 77%) lack BLIMP1 protein expression, despite the presence of BLIMP1 mRNA. These results indicate that a sizable fraction of ABC-DLBCL carry an inactive BLIMP1 gene, and suggest that the same gene is inactivated by epigenetic mechanisms in an additional large number of cases. These findings point to a role for BLIMP1 as a tumor suppressor gene, whose inactivation may contribute to lymphomagenesis by blocking post–GC differentiation of B cells toward plasma cells.


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