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Centrosome aberrations as a possible mechanism for chromosomal instability in non-Hodgkin's lymphoma

Leukemia volume 17, pages 2207–2213 (2003)Cite this article

Abstract

Recently, centrosome aberrations have been described as a possible cause of aneuploidy in many solid tumors. To investigate whether centrosome aberrations occur in non-Hodgkin's lymphoma (NHL) and correlate with histologic subtype, karyotype, and other biological disease features, we examined 24 follicular lymphomas (FL), 18 diffuse large-B-cell lymphomas (DLCL), 33 mantle cell lymphomas (MCL), and 17 extranodal marginal zone B-cell lymphomas (MZBCL), using antibodies to centrosomal proteins. All 92 NHL displayed numerical and structural centrosome aberrations as compared to nonmalignant lymphoid tissue. Centrosome abnormalities were detectable in 32.3% of the cells in NHL, but in only 5.5% of lymphoid cells from 30 control individuals (P<0.0001). Indolent FL and MZBCL contained only 25.8 and 28.8% cells with abnormal centrosomes. In contrast, aggressive DLCL and MCL harbored centrosome aberrations in 41.8 and 35.0% of the cells, respectively (P<0.0001). Centrosomal aberrations correlated to lymphoma grade, mitotic, and proliferation indices, but not to the p53 labeling index. Importantly, diploid MCL contained 31.2% cells with abnormal centrosomes, while tetraploid samples harbored centrosome aberrations in 55.6% of the cells (P<0.0001). These results indicate that centrosome defects are common in NHL and suggest that they may contribute to the acquisition of chromosomal instability typically seen in NHL.

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Acknowledgements

We thank Mrs Brigitte Schreiter, Mrs Christel Kohaut, and Mrs Heike Brückner for excellent technical assistance as well as an anonymous reviewer for thoughtful comments. This work was supported by the Deutsche José Carreras Leukämie-Stiftung eV. (DJCLS 2001/NAT-3), the Deutsche Forschungsgemeinschaft (KR 1981/1-1), and the European Commission ‘Growth program, research project molecular and biological risk factors in mantle cell lymphoma’, Contract Number QLG1-CT-2000-00687. AK is a Heisenberg scholar of the Deutsche Forschungsgemeinschaft.

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Authors and Affiliations

  1. Medizinische Klinik und Poliklinik V, Universität Heidelberg, Heidelberg, Germany

    A Krämer, S Schweizer, C Giesecke & A D Ho

  2. Abteilung Molekulare Genetik, Deutsches Krebsforschungszentrum, Heidelberg, Germany

    K Neben

  3. Institut für Pathologie, Universität Würzburg, Würzburg, Germany

    J Kalla, T Katzenberger, H K Müller-Hermelink & G Ott

  4. Central Unit Biostatistics, Deutsches Krebsforschungszentrum, Heidelberg, Germany

    A Benner

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Krämer, A., Schweizer, S., Neben, K. et al. Centrosome aberrations as a possible mechanism for chromosomal instability in non-Hodgkin's lymphoma. Leukemia 17, 2207–2213 (2003). https://doi.org/10.1038/sj.leu.2403142

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