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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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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DOI: https://doi.org/10.1038/leu.2009.120
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