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Frequent truncating mutations of STAG2 in bladder cancer

Nature Genetics volume 45, pages 1428–1430 (2013)Cite this article

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Abstract

Here we report the discovery of truncating mutations of the gene encoding the cohesin subunit STAG2, which regulates sister chromatid cohesion and segregation, in 36% of papillary non-invasive urothelial carcinomas and 16% of invasive urothelial carcinomas of the bladder. Our studies suggest that STAG2 has a role in controlling chromosome number but not the proliferation of bladder cancer cells. These findings identify STAG2 as one of the most commonly mutated genes in bladder cancer.

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Figure 1: Frequent truncating mutations of STAG2 in urothelial carcinoma of the bladder.
Figure 2: Effects of STAG2 inactivation on proliferation and chromosomal stability in urothelial cancer cells.

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Acknowledgements

We thank B. Vogelstein for assistance in acquiring samples and preparing genomic DNA. This work was supported by US National Institutes of Health grants R01CA169345, R01CA159467 and R21CA143282 to T.W., by the MD Anderson Cancer Center Bladder Cancer SPORE grant P50CA091846 and by the Intramural Research Program of the National Human Genome Research Institute, US National Institutes of Health.

Author information

Author notes

  1. Shahrokh F Shariat

    Present address: Present address: Department of Urology, Medical University of Vienna, Vienna, Austria.,

Authors and Affiliations

  1. Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC, USA

    David A Solomon, Jung-Sik Kim, Julia Gerard & Todd Waldman

  2. Department of Pathology, University of California, San Francisco, San Francisco, California, USA

    David A Solomon & Joanna J Phillips

  3. Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Jolanta Bondaruk, Shizhen Zhang & Bogdan Czerniak

  4. Department of Urology, Weill Cornell College of Medicine, New York, New York, USA

    Shahrokh F Shariat, DaZhong Zhuang, Brian D Robinson & Mark A Rubin

  5. Division of Medical Oncology, Weill Cornell College of Medicine, New York, New York, USA

    Shahrokh F Shariat

  6. Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA

    Zeng-Feng Wang & Markku Miettinen

  7. Cancer Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland, USA

    Abdel G Elkahloun

  8. Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA

    Tomoko Ozawa & C David James

  9. Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Neema Navai

  10. Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Arlene Siefker-Radtke

  11. Department of Pathology, Weill Cornell College of Medicine, New York, New York, USA

    Brian D Robinson & Mark A Rubin

  12. Department of Urology, Hospital Kassel, Kassel, Germany

    Björn Volkmer

  13. Department of Urology, University Hospital Ulm, Ulm, Germany

    Richard Hautmann

  14. Department of Urology, Hospital Am Eichert, Göppingen, Germany

    Rainer Küfer

  15. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

    Pancras C W Hogendoorn

  16. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    George Netto

  17. Department of Surgery, University of Colorado Cancer Center, University of Colorado School of Medicine, Aurora, Colorado, USA

    Dan Theodorescu

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  1. David A Solomon
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Contributions

D.A.S., J.-S.K., J.B., S.F.S., C.D.J., B.C., M.M. and T.W. designed research. D.A.S., J.-S.K., J.B., Z.-F.W., A.G.E., T.O., J.G., D.Z., S.Z. and J.J.P. performed research. J.B., S.F.S., D.Z., M.A.R., B.V., R.H., R.K., P.C.W.H., G.N., D.T., B.C. and M.M. contributed new reagents and analytic tools. D.A.S., J.-S.K., S.F.S., A.G.E., N.N., A.S.-R., B.D.R., C.D.J., M.M. and T.W. analyzed data. D.A.S., S.F.S. and T.W. wrote the manuscript.

Corresponding author

Correspondence to Todd Waldman.

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Competing interests

A provisional patent application has been filed by Georgetown University related to the technology described in this paper on which D.A.S., J.-S.K. and T.W. are the inventors.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–21 and Supplementary Tables 1 and 4–6 (PDF 34619 kb)

Supplementary Table 2

Clinicopathologic characteristics of 111 urothelial carcinomas of the bladder used for STAG2 sequencing. (XLSX 20 kb)

Supplementary Table 3

STAG2 mutations identified in urothelial carcinoma primary tumors and cell lines. (XLSX 13 kb)

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Solomon, D., Kim, JS., Bondaruk, J. et al. Frequent truncating mutations of STAG2 in bladder cancer. Nat Genet 45, 1428–1430 (2013). https://doi.org/10.1038/ng.2800

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