Integrative multi-omics analysis reveals molecular subtypes and tumor evolution of synovial sarcoma

Author:

Chen YiORCID,Su Yanhong,Leo Isabelle RoseORCID,Siavelis Ioannis,Zeng JianmingORCID,Cao Xiaofang,Tsagkozis Panagiotis,Hesla Asle C,Papakonstantinou Andri,Liu Xiao,Huang Wen-Kuan,Ehnman Monika,Johansson HenrikORCID,Lin Yingbo,Lehtiö JanneORCID,Zhang Yifan,Larsson Olle,Haglund de Flon FelixORCID

Abstract

AbstractSynovial sarcomas (SS) are malignant mesenchymal tumors characterized by the SS18-SSX fusion gene, which drives tumorigenesis by altering the composition of the BAF complex. Secondary genomic alterations that determine variations in tumor phenotype or clinical presentation are largely unknown. Herein, we present transcriptome, targeted DNA-sequencing, and proteomics analysis of 91 synovial sarcomas from 55 patients. We identified three SS clusters (SSCs) characterized by distinct histology, tumor microenvironments, genomic complexities, therapeutic effects, and clinical outcomes. Eight BAF complex components are differentially expressed among SSCs, and their role in mesenchymal-epithelial-transition is supported by single cell sequencing. The epithelial cells of biphasic tumors are more susceptible to developing copy number alterations, including amplification of PDCD1 and TMPRSS2. Our findings explain broad concepts in SS biology and imply that the BAF composition at the start of the tumorigenesis (i.e. the cellular linage) may determine the SS subtype, providing a rationale for individualized treatment strategies.

Publisher

Cold Spring Harbor Laboratory

Reference115 articles.

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Sarcoma care in the era of precision medicine;Journal of Internal Medicine;2023-09-07

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