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Frequent truncating mutations of STAG2 in bladder cancer



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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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.

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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.

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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.

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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).

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