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Nat Genet. 2013 Feb;45(2):180-5. doi: 10.1038/ng.2509. Epub 2013 Jan 13.

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

Author information

1
Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

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.

PMID:
23313952
PMCID:
PMC3654808
DOI:
10.1038/ng.2509
[Indexed for MEDLINE]
Free PMC Article

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