1. ¹Klinik für Innere Medizin III, Zentrum für Innere Medizin der Universität Ulm, Ulm, Germany
2. ²Institut für Pathologie, Universität Ulm, Ulm, Germany
3. ³Forschungsdozentur Bioinformatik, Universität Ulm, Ulm, Germany
4. ⁴Abt. Molekulare Genetik, Deutsches Krebsforschungszentrum, Heidelberg, Germany
5. ⁵Städtisches Klinikum Karlsruhe, Karlsruhe, Germany

Correspondence: Dr S Wessendorf, Klinik für Innere Medizin III, Zentrum für Innere Medizin der Universität Ulm, Robert-Koch-Strasse 8, Ulm 89081, Germany. E-mail: swen.wessendorf@uniklinik-ulm.de

⁶These authors contributed equally to this study.

Received 30 May 2007; Revised 25 July 2007; Accepted 26 July 2007; Published online 30 August 2007.

Abstract

Primary mediastinal B-cell lymphoma (PMBL) is an aggressive extranodal B-cell non-Hodgkin's lymphoma with specific clinical, histopathological and genomic features. To characterize further the genotype of PMBL, we analyzed 37 tumor samples and PMBL cell lines Med-B1 and Karpas1106P using array-based comparative genomic hybridization (matrix- or array-CGH) to a 2.8k genomic microarray. Due to a higher genomic resolution, we identified altered chromosomal regions in much higher frequencies compared with standard CGH: for example, +9p24 (68%), +2p15 (51%), +7q22 (32%), +9q34 (32%), +11q23 (18%), +12q (30%) and +18q21 (24%). Moreover, previously unknown small interstitial chromosomal low copy number alterations (for example, -6p21, -11q13.3) and a total of 19 DNA amplifications were identified by array-CGH. For 17 chromosomal localizations (10 gains and 7 losses), which were altered in more than 10% of the analyzed cases, we delineated minimal consensus regions based on genomic base pair positions. These regions and selected immunohistochemistries point to candidate genes that are discussed in the context of NF-B transcription activation, human leukocyte antigen class I/II defects, impaired apoptosis and Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation. Our data confirm the genomic uniqueness of this tumor and provide physically mapped genomic regions of interest for focused candidate gene analysis.