Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma


Uveal melanoma is the most common primary cancer of the eye and often results in fatal metastasis. Here, we describe mutations occurring exclusively at codon 625 of the SF3B1 gene, encoding splicing factor 3B subunit 1, in low-grade uveal melanomas with good prognosis. Thus, uveal melanoma is among a small group of cancers associated with SF3B1 mutations, and these mutations denote a distinct molecular subset of uveal melanomas.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Association of mutation status with clinical outcome in uveal melanoma.

Accession codes

Primary accessions

Gene Expression Omnibus

Sequence Read Archive


  1. Harbour, J.W. Pigment Cell. Melanoma Res. 25, 171–181 (2012).

    CAS  Article  Google Scholar 

  2. Harbour, J.W. et al. Science 330, 1410–1413 (2010).

    CAS  Article  Google Scholar 

  3. Onken, M.D. et al. Invest. Ophthalmol. Vis. Sci. 49, 5230–5234 (2008).

    Article  Google Scholar 

  4. Van Raamsdonk, C.D. et al. Nature 457, 599–602 (2009).

    CAS  Article  Google Scholar 

  5. Papaemmanuil, E. et al. N. Engl. J. Med. 365, 1384–1395 (2011).

    CAS  Article  Google Scholar 

  6. Wang, L. et al. N. Engl. J. Med. 365, 2497–2506 (2011).

    CAS  Article  Google Scholar 

  7. Ellis, M.J. et al. Nature 486, 353–360 (2012).

    CAS  Article  Google Scholar 

  8. Van Raamsdonk, C.D. et al. N. Engl. J. Med. 363, 2191–2199 (2010).

    CAS  Article  Google Scholar 

  9. Golas, M.M., Sander, B., Will, C.L., Luhrmann, R. & Stark, H. Science 300, 980–984 (2003).

    CAS  Article  Google Scholar 

  10. Visconte, V. et al. Blood 120, 3173–3186 (2012).

    CAS  Article  Google Scholar 

  11. An, M. & Henion, P.D. Int. J. Dev. Biol. 56, 223–237 (2012).

    CAS  Article  Google Scholar 

  12. Visconte, V., Makishima, H., Maciejewski, J.P. & Tiu, R.V. Leukemia 26, 2447–2454 (2012).

    CAS  Article  Google Scholar 

  13. Isono, K., Mizutani-Koseki, Y., Komori, T., Schmidt-Zachmann, M.S. & Koseki, H. Genes Dev. 19, 536–541 (2005).

    CAS  Article  Google Scholar 

Download references


This work was supported by US National Institutes of Health (NIH) grants R01 CA16187001 (A.M.B. and J.W.H.) and CA12597007 (J.W.H.), the Melanoma Research Alliance (J.W.H.), the Melanoma Research Foundation (J.W.H.), the Tumori Foundation (J.W.H.), Research to Prevent Blindness, Inc. (J.W.H.) and awards to the Department of Ophthalmology and Visual Sciences at Washington University from a Research to Prevent Blindness, Inc., Unrestricted grant and the US NIH Vision Core grant P30 EY02687c. E.D.O.R. was supported under US NIH training grant 5 T32 AR007279-32. We thank L. Cao for technical assistance and C. Jordan for exome capture. We thank the patients who volunteered to participate in the study in order to make this work possible. This study was approved by the Human Studies Committee at Washington University in St. Louis, and informed consent was obtained from all subjects.

Author information

Authors and Affiliations



J.W.H. participated in the conception and design of the study, provided the samples used in the study, performed biostatistical analysis and drafted the manuscript. E.D.O.R. performed the analysis of next-generation sequencing data and bioinformatics analysis. H.A. performed Sanger sequencing. M.D.O. performed bioinformatics analysis. L.A.W. managed the tissue bank and clinical database and prepared DNA and RNA samples. A.M.B. participated in the conception and design of the study and analyzed the data. All authors contributed to the final draft of the manuscript.

Corresponding authors

Correspondence to J William Harbour or Anne M Bowcock.

Ethics declarations

Competing interests

J.W.H., A.M.B. and Washington University may receive income from the licensing of related technology by Washington University to Castle Biosciences, Inc. This work was not supported by Castle Biosciences, Inc.

Supplementary information

Supplementary Text and Figures

Supplementary Methods, Supplementary Tables 1 and 2 and Supplementary Figures 1–3 (PDF 752 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Harbour, J., Roberson, E., Anbunathan, H. et al. Recurrent mutations at codon 625 of the splicing factor SF3B1 in uveal melanoma. Nat Genet 45, 133–135 (2013).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing