Title | BLIMP1 is a tumor suppressor gene frequently disrupted in activated B cell-like diffuse large B cell lymphoma. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Mandelbaum J, Bhagat G, Tang H, Mo T, Brahmachary M, Shen Q, Chadburn A, Rajewsky K, Tarakhovsky A, Pasqualucci L, Dalla-Favera R |
Journal | Cancer Cell |
Volume | 18 |
Issue | 6 |
Pagination | 568-79 |
Date Published | 2010 Dec 14 |
ISSN | 1878-3686 |
Keywords | Animals, DNA-Binding Proteins, Epigenesis, Genetic, Genes, Tumor Suppressor, Humans, Lymphoma, Large B-Cell, Diffuse, Mice, Mice, Inbred C57BL, Mutation, Missense, Positive Regulatory Domain I-Binding Factor 1, Proto-Oncogene Proteins c-bcl-6, Transcription Factors |
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. |
DOI | 10.1016/j.ccr.2010.10.030 |
Alternate Journal | Cancer Cell |
PubMed ID | 21156281 |
Grant List | CA-37295 / CA / NCI NIH HHS / United States CA-092625 / CA / NCI NIH HHS / United States |
Related Faculty:
Amy Chadburn, M.D.