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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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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DOI: https://doi.org/10.1038/sj.onc.1202842
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