Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing By:Robinson, DR (Robinson, Dan R.)[ 1,2 ] ; Wu, YM (Wu, Yi-Mi)[ 1,2 ] ; Kalyana-Sundaram, S (Kalyana-Sundaram, Shanker)[ 1,2,3 ] ; Cao, XH (Cao, Xuhong)[ 1,4 ] ; Lonigro, RJ (Lonigro, Robert J.)[ 1,5 ] ; Sung, YS (Sung, YunShao)[ 6 ] ; Chen, CL (Chen, Chun-Liang)[ 6 ] ; Zhang, L (Zhang, Lei)[ 6 ] ; Wang, R(Wang, Rui)[ 1,2 ] ; Su, FY (Su, Fengyun)[ 1,2 ] ...More View ResearcherID and ORCID. NATURE GENETICS Volume: 45 Issue: 2 Pages: 180-185 DOI: 10.1038/ng.2509 Published: FEB 2013 View Journal Information 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. Keywords KeyWords Plus:NEGATIVE FEEDBACK LOOP; EXPRESSION; NAB2; EGR1; TRANSCRIPTION; COREPRESSOR; SPECTRUM; CELLS Author Information Reprint Address: Chinnaiyan, AM (reprint author) Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA. Addresses: [ 1 ] Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA [ 2 ] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA [ 3 ] Bharathidasan Univ, Dept Environm Biotechnol, Tiruchchirappalli, Tamil Nadu, India [ 4 ] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA [ 5 ] Univ Michigan, Sch Med, Comprehens Canc Ctr, Ann Arbor, MI USA [ 6 ] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA [ 7 ] Univ Michigan, Ctr Computat Med & Biol, Ann Arbor, MI 48109 USA [ 8 ] Univ Michigan, Sch Med, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI USA [ 9 ] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI USA [ 10 ] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA [ 11 ] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA E-mail Addresses:antonesc@mskcc.org; arul@umich.edu Funding Funding Agency Grant Number National Cancer Institute (NCI) Early Detection Research Network U01 CA111275 National Functional Genomics Center W81XWH-11-1-0520 US Department of Defense US National Institutes of Health through the University of Michigan's Cancer Center Support Grant Linn Fund Cycle for Survival Alan Rosenthal Research Fund for research in sarcoma Weinstein Solitary Fibrous Tumor Research Fund Doris Duke Charitable Foundation Clinical Scientist Award Burroughs Wellcome Foundation Award in Clinical Translational Research View funding text Publisher NATURE PUBLISHING GROUP, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA Categories / Classification Research Areas:Genetics & Heredity Web of Science Categories:Genetics & Heredity Document Information Document Type:Article Language:English Accession Number: WOS:000314333000013 PubMed ID: 23313952 ISSN: 1061-4036 Other Information IDS Number: 081PB Cited References in Web of Science Core Collection: 18 Times Cited in Web of Science Core Collection: 90 5 P30 CA46592 PO1 CA04717915A2 P50 CA 140146-01