title: A novel missense mutation of the XBP1 gene in diffuse large B-cell lymphoma.
abstract: The differentiation of B cells into immunoglobulin-secreting plasma cells is controlled by two transcription factors, B lymphocyte-induced maturation protein 1 (BLIMP1) and X-box-binding protein 1 (XBP1). XBP1 is a positively acting transcription factor in the CREB/ATF family that is expressed at a high level in plasma cells, and Xbp1-deficient mice were devoid of plasma cells, demonstrating that XBP1 is crucial for plasmacytic differentiation. XBP1 acts downstream of BLIMP1 and regulates a variety of genes encoding endoplasmic reticulum-associated proteins. We have previously reported mutations in the PRDM1 gene (previously BLIMP1) in 2 of 15 cases of B-cell lymphoma. Here, we describe a novel mutation in the XBP1 gene in 1 of 5 cases of B-cell lymphoma. A single-base substitution was found in exon 1 (227G>A) of the XBP1 gene in a patient with diffuse large B-cell lymphoma, resulting in a somatic missense mutation (R76K). To date, no mutations in the XBP1 gene in B-cell lymphoma have been reported. Taken together with previous reports, the present results suggest that two key transcription factors for the plasmacytic differentiation, XBP1 and BLIMP1, are involved in the pathogenesis in diffuse large B-cell lymphoma.
authors.affiliation: Department of Pathology, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan. gentate@yahoo.co.jp
authors.forename: Genshu
authors.initials: G
authors.lastname: Tate
authors.forename: Koji
authors.initials: K
authors.lastname: Kishimoto
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hirayama
authors.forename: Takao
authors.initials: T
authors.lastname: Suzuki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Mitsuya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics*; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000605544:Xbp1 protein, mouse