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Uncoupling of genomic instability and tumorigenesis in a mouse model of Burkitt's lymphoma expressing a conditional box II-deleted Myc protein

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Abstract

Burkitt's lymphomas (BL) are characterized by the constitutive expression of c-Myc protein. In total, 50–60% of all BL cells carry mutant c-Myc proteins. Using a mouse model of spontaneously immortalized pro-B-lymphocytes (Ba/F3), we have investigated genomic instability mediated by the conditional expression of either wild-type (WT) or deletion box II Δ106-Myc proteins. We found that both proteins mediate common as well as differing types of chromosomal rearrangements as documented by spectral karyotyping (SKY). A higher level of genomic instability is induced by the Δ106-Myc protein. To examine the tumorigenic potential of WT or Δ106-driven Ba/F3 cells, in vivo tumorigenesis studies were performed in SCID mice. Under the experimental conditions of this study, WT but not Δ106-Myc expressing Ba/F3 cells triggered tumorigenesis in SCID mice. Therefore, the genomic instability phenotype induced by Δ106-Myc can be genetically uncoupled from its tumorigenic potential.

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Acknowledgements

We thank Drs Michael Mowat and Konrad Huppi for stimulating discussions and Ms Mary Cheang for statistical analysis. This work was supported by grants from the Ligue Contre le Cancer comité du Doubs and the Fondation de France, Paris (TF), the Canada Foundation Innovation (CFI) (SM), the Canadian Institutes for Health Research (CIHR) (SM), and The National Science and Engineering Research Council (NSERC) (SM).

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  1. Thierry Fest and Amanda Guffei: These two authors contributed equally to this work

Authors and Affiliations

  1. Manitoba Institute of Cell Biology and The Genomic Center for Cancer Research and Diagnosis, The University of Manitoba, 675 McDermot Avenue, Winnipeg, MB, R3E 0V9, Canada

    Thierry Fest, Amanda Guffei, Santiago Silva & Sabine Mai

  2. Laboratoire universitaire d'hématologie, UPRES 2233-1247, 2 av. Pr. Bernard, 35043, Rennes Cedex, France

    Thierry Fest

  3. Hematopathology Laboratory, Health Sciences centre, Winnipeg, MB, R3A 1R9, Canada

    Gaynor Williams

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  1. Thierry Fest
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  2. Amanda Guffei
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  3. Gaynor Williams
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  4. Santiago Silva
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  5. Sabine Mai
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Correspondence to Thierry Fest or Sabine Mai.

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Fest, T., Guffei, A., Williams, G. et al. Uncoupling of genomic instability and tumorigenesis in a mouse model of Burkitt's lymphoma expressing a conditional box II-deleted Myc protein. Oncogene 24, 2944–2953 (2005). https://doi.org/10.1038/sj.onc.1208467

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  • DOI: https://doi.org/10.1038/sj.onc.1208467

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