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Prepublished online as a Blood First Edition Paper on December 19, 2002; DOI 10.1182/blood-2002-11-3387. This Article Full Text (PDF) Supplemental Spreadsheet All Versions of this Article: 2002-11-3387v1 101/8/2914    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pasqualucci, L. Articles by Dalla-Favera, R. Search for Related Content PubMed PubMed Citation Articles by Pasqualucci, L. Articles by Dalla-Favera, R. Social Bookmarking                   What's this? Submitted November 8, 2002 Accepted November 28, 2002 Mutations of the BCL-6 proto-oncogene disrupt its negative autoregulation in diffuse large B-cell lymphoma Laura Pasqualucci, Anna Migliazza, Katia Basso, Jane Houldsworth, R S K Chaganti, and Riccardo Dalla-Favera* Institute for Cancer Genetics, Columbia University, New York, NY, USA Laboratory of Cancer Genetics and the Department of Medicine, Memorial Sloan-Kettering Cancer Cente, New York, NY, USA * Corresponding author; email: rd10{at}columbia.edu. The BCL6 proto-oncogene encodes a transcriptional repressor whose expression is deregulated by chromosomal translocations in ~40% of diffuse large B-cell lymphoma (DLBCL). The BCL6 regulatory sequences are also targeted by somatic hypermutation in germinal center (GC) B-cells as well as in a fraction of all GC-derived lymphomas. However, the functional consequences of these mutations are not known. Here we report that a subset of mutations specifically associated with DLBCL cause deregulated BCL6 transcription. These mutations affect two adjacent BCL6 binding sites located within the first non-coding exon of the gene and prevent BCL6 from binding its own promoter, thereby disrupting its negative autoregulatory circuit. These alterations were found in ~16% of DLBCL cases devoid of chromosomal translocations involving the BCL6 locus, but not in normal GC B-cells. This study establishes a novel mechanism for BCL6 deregulation and reveals a broader involvement of this gene in DLBCL pathogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Seifert and R. Kuppers Molecular footprints of a germinal center derivation of human IgM+(IgD+)CD27+ B cells and the dynamics of memory B cell generation J. Exp. Med., November 16, 2009; (2009) jem.20091087v1. [Abstract] [Full Text] [PDF] J. X. Zhou, C. H. 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