Document Detail

Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing.
MedLine Citation:
PMID:  23313952     Owner:  NLM     Status:  MEDLINE    
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.
Dan R Robinson; Yi-Mi Wu; Shanker Kalyana-Sundaram; Xuhong Cao; Robert J Lonigro; Yun-Shao Sung; Chun-Liang Chen; Lei Zhang; Rui Wang; Fengyun Su; Matthew K Iyer; Sameek Roychowdhury; Javed Siddiqui; Kenneth J Pienta; Lakshmi P Kunju; Moshe Talpaz; Juan Miguel Mosquera; Samuel Singer; Scott M Schuetze; Cristina R Antonescu; Arul M Chinnaiyan
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-13
Journal Detail:
Title:  Nature genetics     Volume:  45     ISSN:  1546-1718     ISO Abbreviation:  Nat. Genet.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-29     Completed Date:  2013-03-26     Revised Date:  2014-06-24    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  180-5     Citation Subset:  IM    
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MeSH Terms
Base Sequence
Cell Proliferation
Cells, Cultured
Chromatin Immunoprecipitation
DNA Mutational Analysis
Exome / genetics
Fluorescent Antibody Technique
Gene Expression Regulation, Neoplastic / genetics*
Gene Fusion / genetics*
High-Throughput Nucleotide Sequencing
Models, Genetic
Molecular Sequence Data
Real-Time Polymerase Chain Reaction
Regulatory Elements, Transcriptional / genetics*
Repressor Proteins / genetics*
Reverse Transcriptase Polymerase Chain Reaction
STAT6 Transcription Factor / genetics*
Solitary Fibrous Tumors / genetics*
Transcriptome / genetics
Grant Support
5 P30 CA46592/CA/NCI NIH HHS; P01 CA047179/CA/NCI NIH HHS; P01 CA047179-15A2/CA/NCI NIH HHS; P30 CA008748/CA/NCI NIH HHS; P30 CA046592/CA/NCI NIH HHS; P50 CA 140146-01/CA/NCI NIH HHS; P50 CA069568/CA/NCI NIH HHS; P50 CA140146/CA/NCI NIH HHS; U01 CA111275/CA/NCI NIH HHS; U01 CA111275/CA/NCI NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/NAB2 protein, human; 0/Repressor Proteins; 0/STAT6 Transcription Factor; 0/STAT6 protein, human; EC 1.13.12.-/Luciferases
Comment In:
Cancer Discov. 2013 Mar;3(3):OF18   [PMID:  23475888 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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