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Integrative analysis reveals 53BP1 copy loss and decreased expression in a subset of human diffuse large B-cell lymphomas

Oncogene volume 27, pages 318–322 (2008)Cite this article

Abstract

p53-Binding protein 1 (53BP1) encodes a critical checkpoint protein that localizes to sites of DNA double-strand breaks (DSBs) and participates in DSB repair. Mice that are 53bp1 deficient or hemizygous have an increased incidence of lymphoid malignancies. However, 53BP1 abnormalities in primary human tumors have not been described. By combining high-density single nucleotide polymorphism (HD SNP) array data and gene expression profiles, we found 9 of 63 newly diagnosed human diffuse large B-cell lymphomas (DLBCLs) with single copy loss of the chromosome 15q15 region including the 53BP1 locus; these nine tumors also had significantly lower levels of 53BP1 transcripts. 53BP1 single copy loss found with the HD SNP array platform was subsequently confirmed by fluorescence in situ hybridization. These studies highlight the role of 53BP1 copy loss in primary human DLBCLs and the value of integrative analyses in detecting this genetic lesion in human tumors.

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Acknowledgements

This study was supported by grants from National Cancer Institute PO1 CA92625 (KT, SM, JM, JA, FA, TG, MS) and Department of Defense PC040638 (RB).

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Author notes

  1. K Takeyama and S Monti: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    K Takeyama, R Beroukhim & M A Shipp

  2. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA

    S Monti, G Getz, R Beroukhim & T R Golub

  3. Department of Laboratory Medicine, Children's Hospital Boston, MA, USA

    J P Manis & S Dutt

  4. Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA

    P Dal Cin & J C Aster

  5. Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA

    R Beroukhim

  6. and Department of Genetics, Howard Hughes Medical Institute, Children's Hospital, CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA, USA

    F W Alt

  7. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    T R Golub

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  1. K Takeyama
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  2. S Monti
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  9. F W Alt
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Corresponding author

Correspondence to M A Shipp.

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

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Takeyama, K., Monti, S., Manis, J. et al. Integrative analysis reveals 53BP1 copy loss and decreased expression in a subset of human diffuse large B-cell lymphomas. Oncogene 27, 318–322 (2008). https://doi.org/10.1038/sj.onc.1210650

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  • DOI: https://doi.org/10.1038/sj.onc.1210650

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