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Τρίτη 20 Οκτωβρίου 2020

Synovial Sarcoma: A Complex Disease with Multifaceted Signaling and Epigenetic Landscapes

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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.

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