The lesions included in their studies comprised true pericytic tumors, nowadays termed myofibroma myopericytoma, and conventional hemangiopericytoma, which was afterwards accepted as cellular variant of SFT. The unified entity SFT now also contains the lipomatous variant, giant cell ref 1 angiofibroma, and at the malignant end, dedifferentiated SFT showing abrupt transition from classical areas into high grade sarcoma. With the advent of whole genome sequencing, the fusion gene NAB2 STAT6 has been detected as the driver mutation of SFT. NAB2 and STAT6, adjacent genes on 12q13, fuse following genomic inversion of STAT6 with consecutive transcription in a common direction. Expression of the chimeric protein NAB2 STAT6 leads to activation of EGR mediated signaling via distorted NAB2 activity.

Modulation of STAT6 dependent gene expression Inhibitors,Modulators,Libraries seems to be an alternative mechanism but was shown to play a minor role. NAB2 Inhibitors,Modulators,Libraries STAT6 fusion is a distinct molecular feature of SFT since it has not been detected in other tumors and its frequency ranges from 55% to 100%, irrespective of dignity. There are several fusion variants, with conjunction of NAB2 exon 4 STAT6 exon 3 and NAB2 exon 6 STAT6 exon 17 being the most common. In our study, 68% of SFTs carried a NAB2 STAT6 fusion transcript, mostly with a fusion between NAB2 exon 4 and STAT6 exon 3 in accordance with the results by Mohajeri et al. and Barthelmess et al. Negativity for this fusion in 25% of our cases could possibly be explained by alternative or complex genetic rearrangements involving other exons or inversions and deletions, not detectable with our primer combination.

In 2 cases, adequate interpretation of RT PCR results was not possible due to the presence of complex Inhibitors,Modulators,Libraries breakpoints. Furthermore, in single cases other fusion genes have been reported, e. g. STAT6 TRAPPC5 and probably additional fusion genes will be detected in the future. Doyle et al. demonstrated nuclear expression of STAT6 in 98% of a large series of SFTs indicating the presence of the NAB2 STAT6 fusion protein in the nucleus. STAT6 is therefore a highly sensitive and specific immunohistochemical marker for SFT. This is in concert with our results, where 100% of the cases showed strong and diffuse nuclear positivity for STAT6 in comparison to the control group being 100% negative.

Thereby, Inhibitors,Modulators,Libraries STAT6 was diffusely expressed in 7 tumors without a detected NAB2 STAT6 fusion, suspecting limitations in our RT PCR approach in which NAB2 STAT6 fusions could be missed Inhibitors,Modulators,Libraries as mentioned above. Potential diagnostic pitfalls could be STAT6 expression in, for example, the morphologic mimics deep benign fibrous histiocytoma and dedifferentiated liposarcoma, especially in retroperitoneal and abdominal localization. As known, MDM2 and CDK4 immunohistochemistry or MDM2 FISH are useful in identifying dedifferentiated compound libraries liposarcoma. Expression of STAT6 in ca.