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T (brachyury) gene duplication confers major susceptibility to familial chordoma

Nature Genetics volume 41, pages 1176–1178 (2009)Cite this article

Abstract

Using high-resolution array-CGH, we identified unique duplications of a region on 6q27 in four multiplex families with at least three cases of chordoma, a cancer of presumed notochordal origin. The duplicated region contains only the T (brachyury) gene, which is important in notochord development and is expressed in most sporadic chordomas. Our findings highlight the value of screening for complex genomic rearrangements in searches for cancer-susceptibility genes.

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Figure 1: Duplications of 6q27 region in individuals with chordoma from families 1, 3, 4 and 8 detected by custom fine-tiling CGH array.

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Acknowledgements

We thank D. Zametkin for her outstanding skills as a research nurse; G.M. Glenn and M.L. McMaster for their careful clinical evaluations of affected individuals and family members; N.J. Patronas for reviewing the MRIs; A. Bergen and S. Chanock for SNP genotyping; K. Haque and D. Maeder for technical assistance; and, especially, the affected individuals and their families for their participation. This work was supported by the intramural research program of the US National Cancer Institute, Division of Cancer Epidemiology and Genetics, National Institutes of Health; by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development program; and by a grant from the Chordoma Foundation (M.J.K.).

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Author notes

  1. Xiaohong R Yang and David Ng: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Cancer Epidemiology & Genetics, Department of Health and Human Services, Genetic Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

    Xiaohong R Yang, David Ng, Alisa M Goldstein & Dilys M Parry

  2. Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA

    David A Alcorta, Sufeng Li & Michael J Kelley

  3. Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA

    Norbert J Liebsch

  4. St. James University Hospital, Leeds, UK

    Eamonn Sheridan

  5. Durham Veterans Affairs Medical Center, Durham, North Carolina, USA

    Sufeng Li & Michael J Kelley

Authors
  1. Xiaohong R Yang
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  2. David Ng
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  3. David A Alcorta
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  4. Norbert J Liebsch
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  5. Eamonn Sheridan
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  6. Sufeng Li
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  7. Alisa M Goldstein
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  8. Dilys M Parry
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  9. Michael J Kelley
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Contributions

X.R.Y. wrote the first draft of the paper; X.R.Y. and D.N. analyzed the data; D.N., S.L., M.J.K. and D.A.A. performed the laboratory studies, including genotyping, sequencing and breakpoint evaluation; D.N. designed and conducted qPCR analyses; D.M.P. initiated the clinical study and evaluated the chordoma-affected families with D.N.; D.M.P., E.S. and N.J.L. collected the families; X.R.Y., D.N., M.J.K., D.M.P. and A.M.G. planned the work and interpreted the results. All authors contributed to the final version of the paper.

Corresponding author

Correspondence to Dilys M Parry.

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Supplementary Methods, Supplementary Tables 1 and 2 and Supplementary Figures 1–3 (PDF 2096 kb)

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Yang, X., Ng, D., Alcorta, D. et al. T (brachyury) gene duplication confers major susceptibility to familial chordoma. Nat Genet 41, 1176–1178 (2009). https://doi.org/10.1038/ng.454

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