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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 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 Citation Map 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. Related Collections Neoplasia Plenary Papers Oncogenes and Tumor Suppressors Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2003, Vol. 101, No. 8, pp. 2914-2923 PLENARY PAPER Mutations of the BCL6 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 From the Institute for Cancer Genetics and the Departments of Pathology and of Genetics and Development, Columbia University, New York; and the Laboratory of Cancer Genetics and the Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY. The BCL6 proto-oncogene encodes a transcriptional repressor whose expression is deregulated by chromosomal translocations in approximately 40% of diffuse large B-cell lymphomas (DLBCLs). The BCL6 regulatory sequences are also targeted by somatic hypermutation in germinal center (GC) B cells and in a fraction of all GC-derived lymphomas. However, the functional consequences of these mutations are unknown. Here we report that a subset of mutations specifically associated with DLBCL causes deregulated BCL6 transcription. These mutations affect 2 adjacent BCL6 binding sites located within the first noncoding exon of the gene, and they prevent BCL6 from binding its own promoter, thereby disrupting its negative autoregulatory circuit. These alterations were found in approximately 16% of DLBCLs devoid of chromosomal translocations involving the BCL6 locus, but they were not found 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. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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