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Lymphoma

Chromosomal imbalances and partial uniparental disomies in primary central nervous system lymphoma

Leukemia volume 23, pages 1875–1884 (2009)Cite this article

Abstract

To determine the pattern of genetic alterations in primary central nervous system lymphomas (PCNSL), 19 PCNSL were studied by high-density single-nucleotide polymorphism arrays. Recurrent losses involved 6p21.32, 6q21, 8q12–12.2, 9p21.3, 3p14.2, 4q35.2, 10q23.21 and 12p13.2, whereas gains involved 18q21–23, 19q13.31, 19q13.43 and the entire chromosomes X and 12. Partial uniparental disomies (pUPDs) were identified in 6p and 9p21.3. These genomic alterations affected the HLA locus, the CDKN2A/p16, CDKN2B/p15 and MTAP, as well as the PRDM1, FAS, MALT1, and BCL2 genes. Increased methylation values of the CDKN2A/p16 promoter region were detected in 75% (6/8) PCNSL. Gene expression profiling showed 4/21 (20%) minimal common regions of imbalances to be associated with a differential mRNA expression affecting the FAS, STAT6, CD27, ARHGEF6 and SEPT6 genes. Collectively, this study unraveled novel genomic imbalances and pUPD with a high resolution in PCNSL and identified target genes of potential relevance in the pathogenesis of this lymphoma entity.

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Acknowledgements

This study was supported by the Deutsche Krebshilfe/Dr Mildred Scheel Stiftung für Krebsforschung (Grant no. 107733). The Affymetrix and pyrosequencing platforms were provided by the KinderKrebsInitiative Buchholz/Holm-Seppensen.

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Author notes

  1. H Schwindt and I Vater: These authors contributed equally to the work.

  2. M Deckert and R Siebert: These authors share senior authorship.

Authors and Affiliations

  1. Department of Neuropathology, University Hospital of Cologne, Cologne, Germany

    H Schwindt, M Montesinos-Rongen, A Brunn & M Deckert

  2. Institute of Human Genetics, Christian-Albrechts-University Kiel, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    I Vater, J Richter, S Gesk, O Ammerpohl & R Siebert

  3. Institute for Medical Informatics, Statistics and Epidemiology, (IMISE), University of Leipzig, Leipzig, Germany

    M Kreuz & D Hasenclever

  4. German Cancer Research Center, Heidelberg, Germany

    O D Wiestler

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Schwindt, H., Vater, I., Kreuz, M. et al. Chromosomal imbalances and partial uniparental disomies in primary central nervous system lymphoma. Leukemia 23, 1875–1884 (2009). https://doi.org/10.1038/leu.2009.120

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