@article{279dc5cb87fa4f35beed33bb761d8587,
title = "Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing",
abstract = "A 44-year old woman with recurrent solitary fibrous tumor (SFT)/hemangiopericytoma was enrolled in a clinical sequencing program including whole-exome and transcriptome sequencing. A gene fusion of the transcriptional repressor NAB2 with the transcriptional activator STAT6 was detected. Transcriptome sequencing of 27 additional SFTs identified the presence of a NAB2-STAT6 gene fusion in all tumors. Using RT-PCR and sequencing, we detected this fusion in all 51 SFTs, indicating high levels of recurrence. Expression of NAB2-STAT6 fusion proteins was confirmed in SFT, and the predicted fusion products harbor the early growth response (EGR)-binding domain of NAB2 fused to the activation domain of STAT6. Overexpression of the NAB2-STAT6 gene fusion induced proliferation in cultured cells and activated the expression of EGR-responsive genes. These studies establish NAB2-STAT6 as the defining driver mutation of SFT and provide an example of how neoplasia can be initiated by converting a transcriptional repressor of mitogenic pathways into a transcriptional activator.",
author = "Robinson, \{Dan R.\} and Wu, \{Yi Mi\} and Shanker Kalyana-Sundaram and Xuhong Cao and Lonigro, \{Robert J.\} and Sung, \{Yun Shao\} and Chen, \{Chun Liang\} and Lei Zhang and Rui Wang and Fengyun Su and Iyer, \{Matthew K.\} and Sameek Roychowdhury and Javed Siddiqui and Pienta, \{Kenneth J.\} and Kunju, \{Lakshmi P.\} and Moshe Talpaz and Mosquera, \{Juan Miguel\} and Samuel Singer and Schuetze, \{Scott M.\} and Antonescu, \{Cristina R.\} and Chinnaiyan, \{Arul M.\}",
note = "Funding Information: The authors thank T. Barrette for hardware and database management, S. Birkeland, M. Pierce-Burlingame and K. Giles for assistance with sample and manuscript preparation and X. Jing for carrying out microarray experiments. We also thank the larger MI-ONCOSEQ team, including cancer geneticists S. Gruber and J. Innis; bioethicists J.S. Roberts and S.Y. Kim; genetic counselors J. Everett, J. Long and V. Raymond; and radiologists E. Higgins, E. Caoili and R. Dunnick. M. Quist performed initial SNV analysis. L. Sam, A. Balbin and P. Vats assisted with bioinformatics analysis. This project was supported in part by the National Cancer Institute (NCI) Early Detection Research Network (U01 CA111275), the National Functional Genomics Center (W81XWH-11-1-0520) and the US Department of Defense (A.M.C.). Additional infrastructure support was generously provided by the Prostate Cancer Foundation. The work was also supported in part by the US National Institutes of Health through the University of Michigan{\textquoteright}s Cancer Center Support Grant (5 P30 CA46592) and grants PO1 CA047179-15A2 (C.R.A. and S.S.) and P50 CA 140146-01 (C.R.A. and S.S.); the Linn Fund and Cycle for Survival (C.R.A.); the Alan Rosenthal Research Fund for research in sarcoma (C.R.A.); and the Weinstein Solitary Fibrous Tumor Research Fund (C.R.A.). A.M.C. is supported by the Doris Duke Charitable Foundation Clinical Scientist Award and a Burroughs Wellcome Foundation Award in Clinical Translational Research. A.M.C. is an American Cancer Society Research Professor and an A. Alfred Taubman Scholar.",
year = "2013",
month = feb,
doi = "10.1038/ng.2509",
language = "English (US)",
volume = "45",
pages = "180--185",
journal = "Nature genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "2",
}