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Partial uniparental disomy: a recurrent genetic mechanism alternative to chromosomal deletion in malignant lymphoma

Leukemia volume 20, pages 904–905 (2006)Cite this article

Recent studies have highlighted the power of array-based comparative genomic hybridization (aCGH) to characterize chromosomal imbalances in mantle cell lymphoma (MCL).1, 2, 3 Several of the deletions detected in these studies, including losses in 1p, 8p, 9q, 9p, 13q and 17p, have been shown to correlate with prognosis.1, 2 It is widely assumed that chromosomal deletions exert their pathogenic effect through inactivation of tumor suppressor genes. However, novel reports have highlighted partial uniparental disomy (pUPD) as a frequent mechanism of tumor suppressor inactivation in acute leukemias and solid tumors.4, 5, 6 By loss of (part of) one parental chromosome and gain of the homologue from the other parent, pUPD results in loss of heterozygosity (LOH) without chromosomal deletion. As the gene dosage is not altered, pUPD cannot be detected by conventional cytogenetics, fluorescence in situ hybridization or aCGH. To investigate the role of this mechanism in MCL, we have performed genome-wide analyses of single nucleotide polymorphisms (SNPs) using a 100K SNP-array (GeneChip® Human Mapping 100K Set; Affymetrix, Santa Clara, CA, USA) in five t(11;14)-positive MCL cell lines (Granta-519, HBL-2, JEKO, REC-1 and UPN-1), which have been extensively studied by aCGH.2, 7 Copy number and LOH analyses were performed using the Chromosome Copy Number Analysis Tool (version 2.0.0.9, Affymetrix) applying a 0.5 Mb genome smoothing filter.

Partial UPD was defined as a region spanning at least 50 SNPs with homozygous allele calls and a –log10 (P-value) for LOH above 15 in the absence of a deletion.

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References

  1. Kohlhammer H, Schwaenen C, Wessendorf S, Holzmann K, Kestler HA, Kienle D et al. Genomic DNA-chip hybridization in t(11;14)-positive mantle cell lymphomas shows a high frequency of aberrations and allows a refined characterization of consensus regions. Blood 2004; 104: 795–801.

    Article  CAS  Google Scholar 

  2. Rubio-Moscardo F, Climent J, Siebert R, Piris MA, Martin-Subero JI, Nielander I et al. Mantle-cell lymphoma genotypes identified with CGH to BAC microarrays define a leukemic subgroup of disease and predict patient outcome. Blood 2005; 105: 4445–4454.

    Article  CAS  Google Scholar 

  3. Schraders M, Pfundt R, Straatman HM, Janssen IM, van Kessel AG, Schoenmakers EF et al. Novel chromosomal imbalances in mantle cell lymphoma detected by genome-wide array-based comparative genomic hybridization. Blood 2005; 105: 1686–1693.

    Article  CAS  Google Scholar 

  4. Raghavan M, Lillington DM, Skoulakis S, Debernardi S, Chaplin T, Foot NJ et al. Genome-wide single nucleotide polymorphism analysis reveals frequent partial uniparental disomy due to somatic recombination in acute myeloid leukemias. Cancer Res 2005; 65: 375–378.

    CAS  PubMed  Google Scholar 

  5. Fitzgibbon J, Smith LL, Raghavan M, Smith ML, Debernardi S, Skoulakis S et al. Association between acquired uniparental disomy and homozygous gene mutation in acute myeloid leukemias. Cancer Res 2005; 65: 9152–9154.

    Article  CAS  Google Scholar 

  6. Teh MT, Blaydon D, Chaplin T, Foot NJ, Skoulakis S, Raghavan M et al. Genomewide single nucleotide polymorphism microarray mapping in basal cell carcinomas unveils uniparental disomy as a key somatic event. Cancer Res 2005; 65: 8597–8603.

    Article  CAS  Google Scholar 

  7. de Leeuw RJ, Davies JJ, Rosenwald A, Bebb G, Gascoyne RD, Dyer MJ et al. Comprehensive whole genome array CGH profiling of mantle cell lymphoma model genomes. Hum Mol Genet 2004; 13: 1827–1837.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by the Lymphoma Research Foundation (New York). We thank Dr Ali Turhan for allowing to use the UPN-1 cell line. LOH data from BL cell lines were obtained from the Wellcome Trust Sanger Institute Cancer Genome Project website, http://www.sanger.ac.uk/genetics/CGP

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Authors and Affiliations

  1. Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    I Nielaender, J I Martín-Subero & R Siebert

  2. Deutsches Ressourcenzentrum für Genomforschung (RZPD), Berlin, Germany

    F Wagner

  3. Center for Applied Medical Research CIMA, University of Navarra, Pamplona, Spain

    J A Martínez-Climent

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  1. I Nielaender
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  2. J I Martín-Subero
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  5. R Siebert
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Correspondence to R Siebert.

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Nielaender, I., Martín-Subero, J., Wagner, F. et al. Partial uniparental disomy: a recurrent genetic mechanism alternative to chromosomal deletion in malignant lymphoma. Leukemia 20, 904–905 (2006). https://doi.org/10.1038/sj.leu.2404173

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