Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing

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 Pienta, Lakshmi P. Kunju, Moshe Talpaz, Juan Miguel Mosquera, Samuel Singer, Scott M. Schuetze, Cristina R. AntonescuArul M. Chinnaiyan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)180-185
Number of pages6
JournalNature Genetics
Volume45
Issue number2
DOIs
Publication statusPublished - Feb 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

Cite this

Robinson, D. R., Wu, Y. M., Kalyana-Sundaram, S., Cao, X., Lonigro, R. J., Sung, Y. S., ... Chinnaiyan, A. M. (2013). Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing. Nature Genetics, 45(2), 180-185. https://doi.org/10.1038/ng.2509