Ren Chongmin, Liu Jia, Hornicek Francis J, Yue Bin, Duan Zhenfeng
Department of Bone Tumor, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, Shandong 266101, China; Department of Orthopedic Surgery, Sarcoma Biology Laboratory, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Papanicolaou Cancer Research Building, 1550 NW. 10th Avenue, Miami, Florida 33136, USA.
Department of Pediatric Nephrology, Rheumatology and Immunity, The Affiliated Hospital of Qingdao University, No.16 Jiangsu Road, Qingdao, Shandong 266003, China.
Biochim Biophys Acta Rev Cancer. 2024 Nov;1879(6):189215. doi: 10.1016/j.bbcan.2024.189215. Epub 2024 Nov 10.
Synovial sarcoma is a rare type of soft tissue sarcoma that primarily affects adolescents and young adults, featured by aggressive behavior and a high potential for metastasis. Genetically, synovial sarcoma is defined by the fusion oncogene SS18-SSX arising from the translocation of t(X;18)(p11;q11). SS18-SSX fusion gene is the major driver of the oncogenic event in synovial sarcoma. SS18-SSX fusion protein, while not containing any DNA-binding motifs, binds to the SWI/SNF (BAF) complex, a major epigenetic regulator, leading to the disruption of gene expression which results in tumor initiation and progression. Emerging studies on the molecular mechanisms of SS18-SSX associated signaling pathway hold promise for developments in diagnosis and treatments. Advanced diagnostic methods facilitate early and precise detection of the tumor, enabling disease monitoring and prognostic improvements. Treatment of synovial sarcoma typically comprises local surgery, radiotherapy and chemotherapy, while novel managements such as immunotherapy, targeted therapies and epigenetic modifiers are explored. This review focuses on the recent studies of SS18-SSX fusion gene, epigenetic landscape, signaling pathways, diagnostic techniques, and relevant therapeutic advances, aiming to inhibit the oncogenic processes and improve outcomes for patients with synovial sarcoma.
滑膜肉瘤是一种罕见的软组织肉瘤,主要影响青少年和年轻人,其特点是侵袭性强且转移潜力高。在基因方面,滑膜肉瘤由t(X;18)(p11;q11)易位产生的融合癌基因SS18-SSX所定义。SS18-SSX融合基因是滑膜肉瘤致癌事件的主要驱动因素。SS18-SSX融合蛋白虽然不包含任何DNA结合基序,但能与主要的表观遗传调节因子SWI/SNF(BAF)复合物结合,导致基因表达紊乱,从而引发肿瘤的发生和发展。关于SS18-SSX相关信号通路分子机制的新兴研究为诊断和治疗的发展带来了希望。先进的诊断方法有助于早期精确检测肿瘤,实现疾病监测和改善预后。滑膜肉瘤的治疗通常包括局部手术、放疗和化疗,同时也在探索免疫治疗、靶向治疗和表观遗传修饰剂等新的治疗方法。本综述重点关注SS18-SSX融合基因、表观遗传格局、信号通路、诊断技术及相关治疗进展的最新研究,旨在抑制致癌过程并改善滑膜肉瘤患者的治疗效果。