Project description:Meningeal solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that are associated with hematogenous metastasis, and the cell states and spatial transcriptomic architecture of SFTs are unknown. Here we use single-cell and spatial RNA sequencing to show SFTs are comprised of regionally distinct gene expression programs that resemble cerebral vascular development and homeostasis. Our results shed light on mechanisms underlying SFT biology in comparison to other central nervous system tumors and provide a framework for integrating single-cell and spatial transcriptomic data in human cancer samples.
Project description:In this study, we characterize the fusion protein produced by the EPC1-PHF1 translocation in Low Grade Endometrial Stromal Sarcoma (LG-ESS) and Ossifying FibroMyxoid Tumors (OFMT). We express the fusion protein and necessary controls in K562 Cells. The fusion protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 subunits and enzymatic activities and leads to mislocalization of chromatin marks in the genome, linked to aberrant gene expression.
Project description:<p>Transcriptome sequencing of solitary fibrous tumors / hemangiopericytomas from a variety of anatomic sites revealed recurrent gene fusions between two genes, NAB2 and STAT6. All SFTs examined exhibited an in-frame fusion transcript encoding a fusion protein containing the EGR1 interaction domain of NAB2 with the transcriptional activation domain of STAT6. Functional testing of the fusion alleles confirmed the conversion of the wt NAB2 repressor into a transcriptional activator. A range of individual fusion junctions can be detected by next-generation sequencing acro the sample set, highlighting the suitability of this method in the diagnostic characterization of SFTs. This study indentified the pathognomonic alteration in solitary fibrous tumors and illuminates a pathway towards targeted therapeutics for this cancer.</p>
