| Abstract: |
Oncogenesis in synovial sarcoma is driven by the chromosomal translocation t(X,18; p11,q11), which generates an in-frame fusion of the SWI/SNF subunit SS18 to the C-terminal repression domains of SSX1 or SSX2. Proteomic studies have identified an integral role of SS18–SSX in the SWI/SNF complex, and provide new evidence for mistargeting of polycomb repression in synovial sarcoma. Two recent in vivo studies are highlighted, providing additional support for the importance of WNT signaling in synovial sarcoma: One used a conditional mouse model in which knockout of β-catenin prevents tumor formation, and the other used a small-molecule inhibitor of β-catenin in xenograft models. Significance: Synovial sarcoma appears to arise from still poorly characterized immature mesenchymal progenitor cells through the action of its primary oncogenic driver, the SS18–SSX fusion gene, which encodes a multifaceted disruptor of epigenetic control. The effects of SS18–SSX on polycomb-mediated gene repression and SWI/SNF chromatin remodeling have recently come into focus and may offer new insights into the basic function of these processes. A central role for deregulation of WNT–β-catenin signaling in synovial sarcoma has also been strengthened by recent in vivo studies. These new insights into the the biology of synovial sarcoma are guiding novel preclinical and clinical studies in this aggressive cancer. |
| Keywords: |
protein kinase b; protein expression; unclassified drug; gene mutation; review; nonhuman; drug targeting; antineoplastic agent; gene; gene expression; etoposide; notch receptor; transcription factor; cyclophosphamide; proteomics; ifosfamide; carcinogenesis; cixutumumab; docetaxel; temsirolimus; cancer testis antigen; mammalian target of rapamycin; gene fusion; pazopanib; vorinostat; mesenchymal stem cell; synovial sarcoma; anthracycline; beta catenin; chromatin assembly and disassembly; nucleosome; phase 2 clinical trial (topic); phase 1 clinical trial (topic); activating transcription factor 2; pentetic acid; yttrium 90; vismodegib; protein swi; transcription factor snf; wnt signaling pathway; ssx2 gene; ssx1 gene; regorafenib; human; chromosome translocation 18; chromosome translocation x; 3 (2 amino 5 benzoxazolyl) 1 isopropyl 1h pyrazolo[3,4 d]pyrimidin 4 amine; id lv305; lgk974; n (6, 7 dihydro 6 oxo 5h dibenz [b, d] azepin 7 yl) 2, 2 dimethyl n' (2, 2, 3, 3, 3 pentafluoropropyl) propanediamide; otsa101; transducin like enhancer of split 1; cinical feature; epigenetic repression; ss18 gene
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