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A DNA damage repair mechanism is involved in the origin of chromosomal translocations t(4;11) in primary leukemic cells

Oncogene volume 18, pages 4663–4671 (1999)Cite this article

Abstract

Some chromosomal translocations involved in the origin of leukemias and lymphomas are due to malfunctions of the recombinatorial machinery of immunoglobulin and T-cell receptor-genes. This mechanism has also been proposed for translocations t(4;11)(q21;q23), which are regularly associated with acute pro-B cell leukemias in early childhood. Here, reciprocal chromosomal breakpoints in primary biopsy material of fourteen t(4;11)-leukemia patients were analysed. In all cases, duplications, deletions and inversions of less than a few hundred nucleotides indicative of malfunctioning DNA repair mechanisms were observed. We concluded that these translocation events were initiated by several DNA strand breaks on both participating chromosomes and subsequent DNA repair by ‘error-prone-repair’ mechanisms, but not by the action of recombinases of the immune system.

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Acknowledgements

This study was supported by research grants SFB 466C4 and SFB 466C5 from the Deutsche Forschungsgemeinschaft (DFG) to RM/JG and GHF/RM; and research grant 96.047.1 from the Wilhelm Sander Stiftung to RM, JG and GHF. RM was supported by a Career Development Award from the Ria Freifrau von Fritsch Stiftung. Support by the J and F Marohn Foundation is greatfully acknowledged. E Gillert, T Leis, R Repp and M Reichel contributed equally to this work

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Authors and Affiliations

  1. Chair of Genetics, University of Erlangen-Nürnberg, Staudtstr. 5, Erlangen, D-91058, Germany

    Esther Gillert, Martin Reichel, Annette Hösch, Ina Breitenlohner, Sieglinde Angermüller, Georg H Fey & Rolf Marschalek

  2. Department of Pediatrics, Hematology and Oncology, Children's Hospital, University of Gießen, Feulgenstr. 12, Gießen, D-35392, Germany

    Thomas Leis, Arndt Borkhardt, Jochen Harbott & Fritz Lampert

  3. University Hospital, Hematology and Oncology, University of Göttingen, Robert-Kochstr. 40, Göttingen, D-37075, Germany

    Frank Griesinger

  4. Department of Pediatrics, University of Erlangen-Nürnberg, Loschgestr. 15, Erlangen, D-91054, Germany

    Reinald Repp & Johann Greil

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  1. Esther Gillert
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  2. Thomas Leis
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  3. Reinald Repp
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  4. Martin Reichel
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  7. Sieglinde Angermüller
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  8. Arndt Borkhardt
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  11. Frank Griesinger
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  12. Johann Greil
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  13. Georg H Fey
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  14. Rolf Marschalek
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Gillert, E., Leis, T., Repp, R. et al. A DNA damage repair mechanism is involved in the origin of chromosomal translocations t(4;11) in primary leukemic cells. Oncogene 18, 4663–4671 (1999). https://doi.org/10.1038/sj.onc.1202842

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