Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma Journal Article
| Authors: | Pasqualucci, L.; Compagno, M.; Houldsworth, J.; Monti, S.; Grunn, A.; Nandula, S. V.; Aster, J. C.; Murty, V. V.; Shipp, M. A.; Dalla-Favera, R. |
| Article Title: | Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma |
| Abstract: | 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. JEM © The Rockefeller University Press. |
| Keywords: | protein expression; unclassified drug; gene mutation; human cell; frameshift mutation; gene deletion; codon, nonsense; protein domain; protein; cell differentiation; cell line, tumor; b lymphocyte induced maturation protein 1; carcinogenesis; b-lymphocytes; transcription factors; tumor suppressor gene; b cell lymphoma; lymphoma, b-cell; epigenetics; nucleotide sequence; gene inactivation; gene silencing; large cell lymphoma; repressor proteins; nonsense mutation; genes, tumor suppressor; rna splicing; plasma cells; rna splice sites; lymphoma, large-cell, diffuse |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 203 |
| Issue: | 2 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2006-02-20 |
| Start Page: | 311 |
| End Page: | 317 |
| Language: | English |
| DOI: | 10.1084/jem.20052204 |
| PUBMED: | 16492805 |
| PROVIDER: | scopus |
| PMCID: | PMC2118216 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 121" - "Export Date: 4 June 2012" - "CODEN: JEMEA" - "Source: Scopus" |
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