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Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2002-11-3606. This Article Full Text (PDF) All Versions of this Article: 2002-11-3606v1 102/5/1833    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 Gaidano, G. Articles by Dalla-Favera, R. Search for Related Content PubMed PubMed Citation Articles by Gaidano, G. Articles by Dalla-Favera, R. Social Bookmarking                   What's this? Submitted December 3, 2002 Accepted April 10, 2003 Aberrant somatic hypermutation in multiple subtypes of AIDS-associated non-Hodgkin lymphoma Gianluca Gaidano, Laura Pasqualucci, Daniela Capello, Eva Berra, Clara Deambrogi, Davide Rossi, Luigi Maria Larocca, Annunziata Gloghini, Antonino Carbone, and Riccardo Dalla-Favera* Institute for Cancer Genetics, Columbia University, New York, NY, USA Hematology Unit, Division of Internal Medicine, Department of Medical Sciences & IRCAD, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy Institute of Pathology, Catholic University of the Sacred Heart, Rome, Italy Division of Pathology, Centro di Riferimento Oncologicoathology, Istituto Nazionale Tumori, IRCCS, Aviano, Italy * Corresponding author; email: rd10{at}columbia.edu. The pathogenesis of AIDS-related non-Hodgkin lymphomas (AIDS-NHL) is associated with chromosomal translocations that deregulate the expression of various oncogenes. Recently, a novel mechanism of genetic lesion, termed aberrant hypermutation, has been identified in diffuse large B-cell lymphoma (DLBCL) of immunocompetent hosts. In these tumors, the somatic hypermutation process (SHM) that normally targets immunoglobulin V genes (IgV) in B-cells appears to misfire and causes mutations in the 5' sequences of multiple proto-oncogenes, including PIM-1, PAX-5, RhoH/TTF and c-MYC. To investigate whether aberrant hypermutation occurs also in AIDS-NHL, we studied the mutation profile of these four genes in various histologic subtypes. Mutations in 1 gene were detected in 19/39 (48.7%) AIDS-NHL (10/18 AIDS-diffuse large B-cell lymphoma; 4/11 AIDS-Burkitt lymphoma; 4/6 AIDS-primary effusion lymphoma; 1/4 AIDS-primary central nervous system lymphoma), with 9/39 (23.1%) cases carrying mutations in 2 genes. Overall, PIM-1 was mutated in 5/39 (12.8%), PAX-5 in 8/39 (20.5%), RhoH/TTF in 9/39 (23.1%), and c-MYC in 7/27 (25.9%) AIDS-NHL. Mutations were mainly represented by single base-pair substitutions (n = 63) with rare deletions/insertions (n = 5), and displayed features typical of the IgV-associated SHM process. In addition, a number of mutations in PIM-1 and c-MYC were found to affect coding exons, leading to aminoacid substitutions with likely functional consequences. Analysis of intraclonal heterogeneity documented that the aberrant hypermutation activity may be ongoing in at least some cases. These data indicate that aberrant hypermutation is associated with various subtypes of AIDS-NHL and may represent a major contributor to their pathogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Mottok, C. Renne, M. Seifert, E. Oppermann, W. Bechstein, M.-L. Hansmann, R. Kuppers, and A. 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