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Cytogenetics and Molecular Genetics

Further delineation of chromosomal consensus regions in primary mediastinal B-cell lymphomas: an analysis of 37 tumor samples using high-resolution genomic profiling (array-CGH)

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-κB 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.

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Acknowledgements

This work was supported by the Deutsche Krebshilfe Grant 70-2840 Be3 and by the Deutsche José Carreras Stiftung Grant LR02/19. We thankfully acknowledge Zoraja Keresman and Sandra Ruf for excellent technical assistance and Martin JS Dyer, MRC Toxicology Unit, Leicester University, UK for providing Karpas1106P. PACs and BACs for this study were ordered from libraries provided by the Resource Centre/Primary Database of the German Human Genome Project (Berlin, Germany). SW, CS and PM are members of and supported by the German network project molecular mechanisms in malignant lymphoma (MMML).

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Correspondence to S Wessendorf.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu).

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Wessendorf, S., Barth, T., Viardot, A. et al. Further delineation of chromosomal consensus regions in primary mediastinal B-cell lymphomas: an analysis of 37 tumor samples using high-resolution genomic profiling (array-CGH). Leukemia 21, 2463–2469 (2007). https://doi.org/10.1038/sj.leu.2404919

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  • DOI: https://doi.org/10.1038/sj.leu.2404919

Keywords

  • mediastinal B-cell lymphoma
  • array-CGH
  • genomic alterations

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