Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B (original) (raw)

Nature Genetics volume 36, pages 1159–1161 (2004)Cite this article

Abstract

Mosaic variegated aneuploidy is a rare recessive condition characterized by growth retardation, microcephaly, childhood cancer and constitutional mosaicism for chromosomal gains and losses. In five families with mosaic variegated aneuploidy, including two with embryonal rhabdomyosarcoma, we identified truncating and missense mutations of BUB1B, which encodes BUBR1, a key protein in the mitotic spindle checkpoint. These data are the first to relate germline mutations in a spindle checkpoint gene with a human disorder and strongly support a causal link between aneuploidy and cancer development.

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Figure 1: Typical karyotypic abnormalities and BUB1B mutations identified in individuals with MVA.

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Acknowledgements

We thank all the families that gave informed consent to take part in this research; the many clinicians that were involved in their diagnosis and management, including D. Bain, H. Cox, A. Green, A. McEwen, T. Vendrell, P. Ellis and R. Murray; M. Stratton and A. Futreal for advice on the manuscript; and K. Tatton-Brown and T. Min for help in preparation of the figure. A.I. is supported by Tenovus the Cancer Charity. This research was supported and approved by the Institute of Cancer Research (UK).

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Authors and Affiliations

  1. Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK
    Sandra Hanks, Kim Coleman, Sarah Reid, Alexandre Irrthum, Jenny Douglas & Nazneen Rahman
  2. Unitat de Genetica, Hospital Materno-Infantil Vall d'Hebron, Barcelona, Spain
    Alberto Plaja
  3. Medical Genetics Department, Addenbrooke's Hospital, Cambridge, UK
    Helen Firth & Richard Nash
  4. MRC Human Genetics Unit, Edinburgh, Scotland
    David FitzPatrick
  5. Central Regional Genetic Services, Wellington Hospital, Wellington, New Zealand
    Alexa Kidd
  6. Department of Medical Genetics and Child Development, University of Pécs, Hungary
    Károly Méhes
  7. Department for Human Genetics, Case Western Reserve University, Cleveland, Ohio, USA
    Nathanial Robin
  8. West Midland Regional Genetics Service, Birmingham Women's Hospital, Birmingham, UK
    Nora Shannon
  9. Institute of Medical Genetics, Glasgow, Scotland
    John Tolmie
  10. Section of Haemato-oncology, Institute of Cancer Research, Sutton, Surrey, UK
    John Swansbury

Authors

  1. Sandra Hanks
  2. Kim Coleman
  3. Sarah Reid
  4. Alberto Plaja
  5. Helen Firth
  6. David FitzPatrick
  7. Alexa Kidd
  8. Károly Méhes
  9. Richard Nash
  10. Nathanial Robin
  11. Nora Shannon
  12. John Tolmie
  13. John Swansbury
  14. Alexandre Irrthum
  15. Jenny Douglas
  16. Nazneen Rahman

Corresponding author

Correspondence toNazneen Rahman.

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The authors declare no competing financial interests.

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Hanks, S., Coleman, K., Reid, S. et al. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B.Nat Genet 36, 1159–1161 (2004). https://doi.org/10.1038/ng1449

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