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


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.

  • Antonescu CR
  • Cao X
  • Chen CL
  • Chinnaiyan AM
  • Iyer MK
  • Kalyana-Sundaram S
  • Kunju LP
  • Lonigro RJ
  • Mosquera JM
  • Pienta KJ
  • Robinson DR
  • Roychowdhury S
  • Schuetze SM
  • Siddiqui J
  • Singer S
  • Su F
  • Sung YS
  • Talpaz M
  • Wang R
  • Wu YM
  • Zhang L
PubMed ID
Appears In
Nat Genet, 2013, 45 (2)