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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.

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

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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.

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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.

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Correspondence to J William Harbour or Anne M Bowcock.

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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.

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

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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).

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