Synovial Sarcoma: A Complex Disease with Multifaceted Signaling and Epigenetic Landscapes
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SARCOMAS (SR PATEL, SECTION EDITOR)
Synovial Sarcoma: A Complex Disease with Multifaceted Signaling and Epigenetic Landscapes Marc El Beaino 1,2,3
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Elie Rassy 4
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Bana Hadid 2 & Dejka M. Araujo 5 & Nicholas Pavlidis 6
&
Patrick P. Lin 1
Accepted: 7 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
ABSTRACT Purpose of Review Aside from a characteristic SS18–SSX translocation identified in almost all cases, no genetic anomalies have been reliably isolated yet to drive the pathogenesis of synovial sarcoma. In the following review, we explore the structural units of wild-type SS18 and SSX, particularly as they relate to the transcriptional alterations and cellular pathway changes imposed by SS18–SSX. Recent Findings Native SS18 and SSX contribute recognizable domains to the SS18–SSX chimeric proteins, which inflict transcriptional and epigenetic changes through selective protein interactions involving the SWI/SNF and Polycomb chromatin remodeling complexes. Multiple oncogenic and developmental pathways become altered, collectively reprogramming the cellular origin of synovial sarcoma and promoting its malignant transformation. Summary Synovial sarcoma is characterized by complex epigenetic and signaling landscapes. Identifying the operational pathways and concomitant genetic changes induced by SS18–SSX fusions could help develop tailored therapeutic strategies to ultimately improve disease control and patient survivorship. Keywords Synovial sarcoma . neoplastic pathways . SS18–SSX . SWI/SNF complex . Polycomb complex . chromatin modulation
Introduction Synovial sarcoma is a rare soft-tissue malignancy that grows predominantly in the lower limbs of young adults [1, 2]. In This article is part of the Topical Collection on Sarcomas * Marc El Beaino [email protected] 1
Department of Orthopaedic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
2
Department of Orthopaedic Surgery and Rehabilitation Medicine, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA
3
School of Public Health, State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA
4
Department of Cancer Medicine, Gustave Roussy Institute, F-94805 Villejuif, France
5
Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
6
Department of Medical Oncology, University of Ioannina, 451 Ioannina, Greece
spite of its name, it does not stem from the synovium and cumulative evidence points towards a mesenchymal origin for the disease [3–8]. The tumor harbors a stable karyotype with few secondary cytogenetic alterations [9, 10, 11•, 12••]. It is driven by a unique genetic exchange that fuses the SS18 gene with an SSX partner [13, 14]. The ensuing SS18–SSX translocation is the only recurring genetic event reliably isolated in almost all cases and encodes chimeric proteins that modulate transcriptional and epigenetic pathways through precise protein interactions [13, 15–20]. Current
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