Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing Academic Article uri icon

Overview

MeSH Major

  • Gene Expression Regulation, Neoplastic
  • Gene Fusion
  • Regulatory Elements, Transcriptional
  • Repressor Proteins
  • STAT6 Transcription Factor
  • Solitary Fibrous Tumors

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.

publication date

  • February 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3654808

Digital Object Identifier (DOI)

  • 10.1038/ng.2509

PubMed ID

  • 23313952

Additional Document Info

start page

  • 180

end page

  • 5

volume

  • 45

number

  • 2