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Cancer predisposition caused by elevated mitotic recombination in Bloom mice

Nature Genetics volume 26, pages 424–429 (2000)Cite this article

Abstract

Bloom syndrome is a disorder associated with genomic instability that causes affected people to be prone to cancer. Bloom cell lines show increased sister chromatid exchange, yet are proficient in the repair of various DNA lesions. The underlying cause of this disease are mutations in a gene encoding a RECQ DNA helicase. Using embryonic stem cell technology, we have generated viable Bloom mice that are prone to a wide variety of cancers. Cell lines from these mice show elevations in the rates of mitotic recombination. We demonstrate that the increased rate of loss of heterozygosity (LOH) resulting from mitotic recombination in vivo constitutes the underlying mechanism causing tumour susceptibility in these mice.

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Figure 1: Gene targeting at the mouse Blm locus.
Figure 2: Characterization of the Blmm2 and Blmm3 mutant alleles.
Figure 3: The effect of Blm deficiency on SCE.
Figure 4: Tumours in Blmm3/m3 mice.
Figure 5: The effect of Blm deficiency on gene targeting.
Figure 6: The effect of Blm deficiency on LOH in ES cells.
Figure 7: The effect of Blm deficiency on tumour susceptibility in ApcMin mice.

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Acknowledgements

We thank P. Biggs for comments on the manuscript. A.B. acknowledges support from the National Cancer Institute.

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Author notes

  1. Guangbin Luo

    Present address: Department of Genetics and the Ireland Cancer Center, Case Western Reserve University School of Medicine, University Hospital of Cleveland, Cleveland, Ohio, USA

  2. Allan Bradley

    Present address: The Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

  3. Guangbin Luo and Irma M. Santoro: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA

    Guangbin Luo, Irma M. Santoro, Ichiko Nishijima, Michael Mills, Hagop Youssoufian & Allan Bradley

  2. Department of Pathology, Baylor College of Medicine, Houston, Texas, USA

    Hannes Vogel

  3. Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA

    Allan Bradley

  4. McDermott Center for Human Growth and Development, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA

    Lisa D. McDaniel & Roger A. Schultz

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Correspondence to Allan Bradley.

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Luo, G., Santoro, I., McDaniel, L. et al. Cancer predisposition caused by elevated mitotic recombination in Bloom mice. Nat Genet 26, 424–429 (2000). https://doi.org/10.1038/82548

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