Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing Journal Article
| Authors: | Robinson, D. R.; Wu, Y. M.; Kalyana-Sundaram, S.; Cao, X.; Lonigro, R. J.; Sung, Y. S.; Chen, C. L.; Zhang, L.; Wang, R.; Su, F.; Iyer, M. K.; Roychowdhury, S.; Siddiqui, J.; Pienta, K. J.; Kunju, L. P.; Talpaz, M.; Mosquera, J. M.; Singer, S.; Schuetze, S. M.; Antonescu, C. R.; Chinnaiyan, A. M. |
| Article 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. © 2013 Nature America, Inc. All rights reserved. |
| Keywords: | adolescent; adult; child; clinical article; controlled study; school child; aged; unclassified drug; gene mutation; gene sequence; cancer recurrence; cell proliferation; gene overexpression; reverse transcription polymerase chain reaction; transcription factor; cell culture; gene fusion; solitary fibrous tumor; transcriptome; stat6 protein; transcription factor nab2; early growth response factor |
| Journal Title: | Nature Genetics |
| Volume: | 45 |
| Issue: | 2 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2013-02-01 |
| Start Page: | 180 |
| End Page: | 185 |
| Language: | English |
| DOI: | 10.1038/ng.2509 |
| PROVIDER: | scopus |
| PUBMED: | 23313952 |
| PMCID: | PMC3654808 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 March 2013" - "CODEN: NGENE" - "Source: Scopus" |
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