title: Conditional inactivation of p53 in mature B cells promotes generation of nongerminal center-derived B-cell lymphomas.
abstract: The p53 tumor suppressor exerts a central role in protecting cells from oncogenic transformation. Accordingly, the p53 gene is mutated in a large number of human cancers. In mice, germ-line inactivation of p53 confers strong predisposition to development of different types of malignancies, but the early onset of thymic lymphomas in the majority of the animals prevents detailed studies of tumorigenesis in other tissues. Here, we use the Cre/Lox approach to inactivate p53 in mature B cells in mice (referred to as "CP" B cells) and find that such p53 inactivation results in the routine development of IgM-positive CP peripheral B-cell lymphomas. The CP lymphomas generally appear to arise, even in mice subjected to immunization protocols to activate germinal center reaction, from naive B cells that had not undergone immunoglobulin (Ig) heavy chain gene class switching or somatic hypermutation. In contrast to thymic lymphomas that arise in p53-deficient mice, which generally lack clonal translocations, nearly all analyzed CP B-cell tumors carried clonal translocations. However, in contrast to spontaneous translocations in other mouse B-cell tumor models, CP B-cell tumor translocations were not recurrent and did not involve Ig loci. Therefore, CP tumors might provide models for human lymphomas lacking Ig translocations, such as splenic marginal zone B-cell lymphoma or Waldenstrom macroglobulinemia. Our studies indicate that deletion of p53 is sufficient to trigger transformation of mature B cells and support the notion that p53 deficiency may allow accumulation of oncogenic translocations in B cells.
authors: Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
authors: Monica
authors: M
authors: Gostissa
authors: Julia M
authors: JM
authors: Bianco
authors: Daniel J
authors: DJ
authors: Malkin
authors: Jeffery L
authors: JL
authors: Kutok
authors: Scott J
authors: SJ
authors: Rodig
authors: Herbert C
authors: HC
authors: Morse
authors: Craig H
authors: CH
authors: Bassing
authors: Frederick W
authors: FW
authors: Alt
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D015139:Blotting, Southern; D017931:DNA Primers; D005434:Flow Cytometry; D020868:Gene Silencing; D016158:Genes, p53; D017404:In Situ Hybridization, Fluorescence; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D014178:Translocation, Genetic
chemical_list: D017931:DNA Primers
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