Identification of Recurrent NAB2-STAT6 Gene Fusions in Solitary Fibrous Tumor by Integrative Sequencing
By D. Robinson, Yi-Mi Wu, Shanker Kalyana-Sundaram, Xuhong Cao, R. Lonigro, Yun‐Shao Sung, Chun‐Liang Chen, Lei Zhang, Rui Wang, Fengyun Su and 11 more. Nature Genetics, 2013
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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.
Subfields: Oral Surgery, Pulmonary and Respiratory Medicine, Rheumatology
View Paper: https://www.semanticscholar.org/paper/b2c2fd9594bd74a2630e8ed9fb27771d82f3c3b1
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In Rheumatology
Citations in the corpus
- Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors. (2014, background): “NAB2-STAT6 gene fusions in solitary fibrous tumor (SFT)/hemangiopericytoma [22], STAT3 mutations in T large granular lymphocytic leukemia [23] and STAT5b mutations in large granular lymphocytic leukemia [24].”
- The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary (2016, background): “Nonetheless, both solitary fibrous tumors and hemangiopericytomas, including those occurring in the neuraxis, share inversions at 12q13, fusing the NAB2 and STAT6 genes [8, 41], which leads to STAT6 nuclear expression that can be detected by immunohistochemistry [45].”