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Identification of Recurrent NAB2-STAT6 Gene Fusions in Solitary Fibrous Tumor by Integrative Sequencing

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 J Pienta, etc.

Nat Genet. 2013 Feb;45(2):180-5.

PMID: 23313952

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1504588004	NAB2		1504588-00-4	Price

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