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Chromosomal Breakpoints Affecting Immunoglobulin Loci Are Recurrent in Hodgkin and Reed-Sternberg Cells of Classical Hodgkin Lymphoma

Institutes of ¹ Human Genetics and ² Hematopathology and ³ Department of Pediatrics, University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany; ⁴ Service d'Hématologie Biologique and ⁵ Pathology Service, Centre Hospitalier Lyon Sud, Lyon, France; ⁶ Laboratoire de Genetique Oncologique, Centre Henri-Becquerel, Rouen, France; ⁷ Institute for Cell Biology (Tumor Research), University of Duisburg-Essen, Medical School, Essen, Germany; ⁸ Institute for Pathology, University of Ulm, Ulm, Germany; ⁹ Institute of Pathology, Medical University of Lübeck, Lübeck, Germany; ¹⁰ Pathology Department, National Hematology Research Center, Moscow, Russia; ¹¹ Institute of Pathology, University of Würzburg, Würzburg, Germany; ¹² Department of Pathology, Charite-University Medicine, Campus Benjamin Franklin, Berlin, Germany; and ¹³ Senckenberg Institute of Pathology, University of Frankfurt, Frankfurt am Main, Germany

Requests for reprints: Reiner Siebert, Institute of Human Genetics, University Hospital Schleswig-Holstein Campus Kiel, Schwanenweg 24, 24105 Kiel, Germany. Phone: 49-431-597-1779; Fax: 49-431-597-1880; E-mail: rsiebert{at}medgen.uni-kiel.de.

Chromosomal breakpoints affecting immunoglobulin (IG) loci are recurrent in many subtypes of B-cell lymphomas. However, despite the predominant B-cell origin of the Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL), the presence of chromosomal translocations in IG loci has not yet been systematically explored. Therefore, we have investigated a series of cHL for chromosomal breakpoints in the IGH (n = 230), IGL (n = 139), and IGK (n = 138) loci by interphase cytogenetics. Breakpoints in the IGH, IGL, or IGK locus were observed in the HRS cells of 26 of 149 (17%), 2 of 70, and 1 of 77 evaluable cHLs, respectively. The IG partners could be identified in eight cHLs and involved chromosomal bands 2p16 (REL), 3q27 (BCL6, two cases), 8q24.1 (MYC), 14q24.3, 16p13.1, 17q12, and 19q13.2 (BCL3/RELB). In 65 of 85 (76%) cHLs evaluable for an IGH triple-color probe, the HRS cells showed evidence for a (partial) deletion of the IGH constant region, suggesting the presence of class switch recombination (CSR). Furthermore, analyses with this probe in cases with IGH breakpoints indicated that at least part of them seem to be derived from CSR defects. Our results show that chromosomal breakpoints affecting the IG loci are recurrent in cHL. (Cancer Res 2006; 66(21): 10332-8)

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