sequencing heredity

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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
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NATURE GENETICS
Volume: 45
Issue: 2
Pages: 180-185
DOI: 10.1038/ng.2509
Published: FEB 2013
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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
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