| Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing. | |
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MedLine Citation:
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PMID: 23313952 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2013-01-13 |
Journal Detail:
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Title: Nature genetics Volume: 45 ISSN: 1546-1718 ISO Abbreviation: Nat. Genet. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-29 Completed Date: 2013-03-26 Revised Date: 2013-05-16 |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: United States |
Other Details:
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Languages: eng Pagination: 180-5 Citation Subset: IM |
Affiliation:
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Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Base Sequence Cell Proliferation Cells, Cultured Chromatin Immunoprecipitation DNA Mutational Analysis Exome / genetics Female Fluorescent Antibody Technique Gene Expression Regulation, Neoplastic / genetics* Gene Fusion / genetics* High-Throughput Nucleotide Sequencing Humans Immunoblotting Luciferases 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 | |
ID/Acronym/Agency:
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5 P30 CA46592/CA/NCI NIH HHS; P01 CA047179-15A2/CA/NCI NIH HHS; P50 CA 140146-01/CA/NCI NIH HHS; P50 CA069568/CA/NCI NIH HHS; U01 CA111275/CA/NCI NIH HHS; U01 CA111275/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/NAB2 protein, human; 0/Repressor Proteins; 0/STAT6 Transcription Factor; 0/STAT6 protein, human; EC 1.13.12.-/Luciferases |
| Comments/Corrections | |
Comment In:
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Cancer Discov. 2013 Mar;3(3):OF18
[PMID:
23475888
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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