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Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors

Abstract

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors. Here, we describe the identification of a NAB2-STAT6 fusion from whole-exome sequencing of 17 SFTs. Analysis in 53 tumors confirmed the presence of 7 variants of this fusion transcript in 29 tumors (55%), representing a lower bound for fusion frequency at this locus and suggesting that the NAB2-STAT6 fusion is a distinct molecular feature of SFTs.

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Figure 1: Structure of the NAB2-STAT6 fusion.

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Acknowledgements

We are grateful to the individuals with SFT who contributed material for this study. We thank members of the Genomics Platform at the Broad Institute for their technical expertise and M. Abazeed and A. Dulak for critically reviewing the manuscript. This work was conducted as part of the Slim Initiative for Genomic Medicine in the Americas (SIGMA), a project funded by the Carlos Slim Health Institute in Mexico. This work was supported by a Specialized Program of Research Excellence (SPORE) grant in Soft Tissue Sarcoma (P50 CA140146) and a P01 grant (P01CA47179) to S. Singer (MSKCC). J.C. is supported by an American Cancer Society AstraZeneca Postdoctoral Fellowship. A.M.C. is supported by a grant from the Kristen Ann Carr Foundation. M.M. is supported by generous donations from M.B. Zuckerman and Team Dragonfly of the Pan-Mass Challenge. Material was collected under institutional review board (IRB)-approved protocols at the Memorial Sloan-Kettering Cancer Center and the Oregon Health & Science University Biolibrary. All patients provided informed consent.

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Contributions

J.C. and M.M. conceived the project. J.C., A.M.C. and M.M. wrote the manuscript with input from all coauthors. J.C., A.M.C. and R.O. performed experiments. J.C. and M.R. performed computational analyses. A.M. contributed an unpublished algorithm to the analysis. J.C., A.M.C., M.R., S.R.W., R.O., D.A.F. and M.M. analyzed the results. A.M.C. and M.C.H. contributed samples. L.A. and D.A. facilitated the transfer, sequencing and analysis of samples.

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Correspondence to Matthew Meyerson.

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Competing interests

M.M. is a paid consultant for and equity holder in Foundation Medicine, a genomics-based oncology diagnostics company, and is a paid consultant for Novartis. M.C.H. is a paid consultant for and equity holder in Molecular MD, a molecular diagnostics company, and is a paid consultant for Novartis.

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Supplementary Methods, Supplementary Figures 1–4 and Supplementary Tables 1–5 (PDF 2583 kb)

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Chmielecki, J., Crago, A., Rosenberg, M. et al. Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors. Nat Genet 45, 131–132 (2013). https://doi.org/10.1038/ng.2522

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