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Blood, 1 August 2006, Vol. 108, No. 3, pp. 1013-1020. Prepublished online as a Blood First Edition Paper on April 13, 2006; DOI 10.1182/blood-2005-10-3949. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: 2005-10-3949v1 108/3/1013    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 Liso, A. Articles by Falini, B. Search for Related Content PubMed PubMed Citation Articles by Liso, A. Articles by Falini, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 3, 2005 Accepted March 14, 2006 Aberrant somatic hypermutation in tumor cells of nodular lymphocyte-predominant and classical Hodgkin's lymphoma Arcangelo Liso, Daniela Capello, Teresa Marafioti, Enrico Tiacci, Michaela Cerri, Verena Distler, Marco Paulli, Antonino Carbone, Georges Delsol, Elias Campo, Stefano Pileri, Laura Pasqualucci, Gianluca Gaidano, and Brunangelo Falini* Institute of Hematology, University of Perugia, Perugia, Italy; Institute of Hematology, University of Foggia, Foggia, Italy Division of Hematology, Department of Clinical and Experimental Medicine & IRCAD, Italy Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford, United Kingdom Institute of Hematology, University of Perugia, Perugia, Italy Institute of Pathology, University of Frankfurt, Essen, Germany; Section of Molecular Genetics, Institute for Cell Biology-Tumor Research, University of Duisburg-Essen, Medical School, Essen, Germany Anatomic Pathology Department, IRCCS Policlinico S. Matteo, Pavia, Italy Dipartimento di Anatomic Patologica, Instituto Nazionale Tumori, Milano, Italy Centre de Physiopathologie de Toulouse Purpan, CPTP INSERM U563, CHU Pupan, France Hematophatology Section, University of Barcelona, Spain Hematophatology Section, Policlinico S. Orsola, Bologna, Italy Institute of Hematology, University of Perugia, Perugia, Italy; Institute for Cancer Genetics, Columbia University, New York, USA * Corresponding author; email: faliniem{at}unipg.it. Aberrant somatic hypermutation (SHM) has been identified as a mechanism for genome-wide instability in diffuse large B-cell lymphoma (DLBCL). To assess whether aberrant SHM plays a role in the molecular pathogenesis of Hodgkin lymphoma (HL), we investigated microdissected neoplastic cells of nodular lymphocyte predominant (NLPHL) (n=10) and classical cHL (n=9) for the presence of mutations in the 5 sequences of four previously identified aberrant SHM targets (PIM1, PAX5, RhoH/TTF and cMYC). Mutations in one or more genes were detected in 80% NLPHL and 55% cHL, with 50% and 30% of cases carrying mutations in two or more genes, respectively. The most frequently involved proto-oncogene was PAX5, mutated in 7/9 NLPHL and 2/9 cHL. In total n=34 mutations were detected in NLPHL (frequency 1.04/1000bp) and n=35 in cHL (frequency 1.92/1000bp). Mutations were of somatic origin, since they were absent in control T cells and shared most of the features of immunoglobulin variable (IGV) genes-associated SHM mechanism, i.e. single nucleotide substitutions (n=63) with rare deletions/insertions (n=6), and a predominance of transitions over transversions with preferential targeting motifs. Our finding that, similarly to DLBCL, NLPHL and in cHL are targeted by aberrant SHM, suggests that these lymphomas may share common molecular pathogenetic events. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. 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