title: BLIMP1 is a tumor suppressor gene frequently disrupted in activated B cell-like diffuse large B cell lymphoma.
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.
authors.affiliation: Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mandelbaum
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.forename: Hongyan
authors.initials: H
authors.lastname: Tang
authors.forename: Tongwei
authors.initials: T
authors.lastname: Mo
authors.forename: Manisha
authors.initials: M
authors.lastname: Brahmachary
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shen
authors.forename: Amy
authors.initials: A
authors.lastname: Chadburn
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
authors.forename: Alexander
authors.initials: A
authors.lastname: Tarakhovsky
authors.forename: Laura
authors.initials: L
authors.lastname: Pasqualucci
authors.forename: Riccardo
authors.initials: R
authors.lastname: Dalla-Favera
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D044127:Epigenesis, Genetic; D016147:Genes, Tumor Suppressor; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000209:etiology / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D020125:Mutation, Missense; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; C513258:Prdm1 protein, mouse; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1