Molecular and epigenetic oncogenesis in synovial sarcoma: implications for cancer biology, diagnosis and treatment

IF 7.3 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Oncogene Pub Date : 2025-08-23 DOI:10.1038/s41388-025-03547-1

Amy Xueqi Wang, Kevin B. Jones, Torsten O. Nielsen

引用次数: 0

Abstract

The SS18::SSX oncogene is the driver of synovial sarcoma, an aggressive cancer presenting in young adults that has poor long-term outcomes. Over the past five years, significant progress has been made in understanding the molecular, genomic, and epigenetic mechanisms underlying synovial sarcoma. This review synthesizes recent advancements in synovial sarcoma, including diagnostic pathology, genomic profiling, SS18::SSX biology, epigenetic dysregulation, proteomics, targetable pathways and immunotherapy. Key findings include the identification of rare but instructive alternative gene fusions, the roles of PRC1 and of liquid-liquid phase separation in SS18::SSX-mediated oncogenesis, and the development of epigenetic and engineered T-cell therapies. These advances offer new hope for improved treatments and outcomes in synovial sarcoma patients, though challenges remain in overcoming resistance and ensuring equitable access to emerging therapies.

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滑膜肉瘤的分子和表观遗传肿瘤发生：对癌症生物学、诊断和治疗的意义。

SS18::SSX癌基因是滑膜肉瘤的驱动因子，滑膜肉瘤是一种侵袭性癌症，多发于年轻人，长期预后较差。在过去的五年中，在了解滑膜肉瘤的分子、基因组和表观遗传机制方面取得了重大进展。本文综述了滑膜肉瘤的最新进展，包括诊断病理学、基因组分析、SS18::SSX生物学、表观遗传失调、蛋白质组学、靶向途径和免疫治疗。主要发现包括鉴定罕见但具有指导意义的替代基因融合，PRC1和液-液相分离在SS18:: ssx介导的肿瘤发生中的作用，以及表观遗传和工程化t细胞治疗的发展。这些进展为改善滑膜肉瘤患者的治疗和预后提供了新的希望，尽管在克服耐药性和确保公平获得新疗法方面仍然存在挑战。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncogene 医学-生化与分子生物学

CiteScore

15.30

自引率

1.20%

发文量

404

审稿时长

1 months

期刊介绍： Oncogene is dedicated to advancing our understanding of cancer processes through the publication of exceptional research. The journal seeks to disseminate work that challenges conventional theories and contributes to establishing new paradigms in the etio-pathogenesis, diagnosis, treatment, or prevention of cancers. Emphasis is placed on research shedding light on processes driving metastatic spread and providing crucial insights into cancer biology beyond existing knowledge. Areas covered include the cellular and molecular biology of cancer, resistance to cancer therapies, and the development of improved approaches to enhance survival. Oncogene spans the spectrum of cancer biology, from fundamental and theoretical work to translational, applied, and clinical research, including early and late Phase clinical trials, particularly those with biologic and translational endpoints.