Dataset Information

Molecular Profiling Defines Three Subtypes of Synovial Sarcoma

ABSTRACT: Synovial Sarcomas (SS) are characterized by the presence of the SS18::SSX fusion gene, which protein product induce chromatin changes through remodeling of the BAF complex (BRG1/BRM-associated factor complex), which leads to widespread alterations in gene expression that drive tumor development and progression. However, there are no comprehensive studies that integrate multi-omics approaches to fully understand the heterogeneity and molecular subtypes of SS. To elucidate the genomic events that drive phenotypic diversity in SS, we performed RNA and targeted DNA sequencing on 91 tumors from 55 patients. Our results were verified by proteomic analysis, public gene expression cohorts and single-cell RNA sequencing. Transcriptome profiling identified three distinct SS subtypes resembling the known histological subtypes: SS subtype I and was characterized by hyperproliferation, evasion of immune detection and a poor prognosis. SS subtype II and was dominated by a vascular-stromal component and had a significantly better outcome. SS Subtype III was characterized by biphasic differentiation, increased genomic complexity and immune suppression mediated by checkpoint inhibition, and poor prognosis despite good responses to neoadjuvant therapy. Chromosomal abnormalities were an independent significant risk factor for metastasis. KRT8 was identified as a key component for epithelial differentiation in biphasic tumors, potentially controlled by OVOL1 regulation. Our multi-omics analysis revealed biological and genetic variability between these subtypes, including key transcriptome patterns and secondary genomic events such as copy number alterations, could be associated with long-term outcomes. Our findings explain the histological grounds for SS classification and indicate that a significantly larger proportion of patients have high risk tumors (corresponding to SS subtype I) than previously believed.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Georgios Mermelekas

LAB HEAD: Janne Lehtiö

PROVIDER: PXD053789 | Pride | 2025-05-07

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Protein_group_RNAseq_overlap_3-10.xlsx	Xlsx
	SS_DEqMS_FGSEA.xlsx	Xlsx
	XCFHYC_20210929_SS_TMT16_320ug_IPG3-10_set1_fr02.raw	Raw
	XCFHYC_20210929_SS_TMT16_320ug_IPG3-10_set1_fr03.raw	Raw
	XCFHYC_20210929_SS_TMT16_320ug_IPG3-10_set1_fr04.raw	Raw

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Molecular Profiling Defines Three Subtypes of Synovial Sarcoma.

Chen Yi Y Su Yanhong Y Cao Xiaofang X Siavelis Ioannis I Leo Isabelle Rose IR Zeng Jianming J Tsagkozis Panagiotis P Hesla Asle C AC Papakonstantinou Andri A Liu Xiao X Huang Wen-Kuan WK Zhao Binbin B Haglund Cecilia C Ehnman Monika M Johansson Henrik H Lin Yingbo Y Lehtiö Janne J Zhang Yifan Y Larsson Olle O Li Xuexin X de Flon Felix Haglund FH

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20240910 41

Synovial Sarcomas (SS) are characterized by the presence of the SS18::SSX fusion gene, which protein product induce chromatin changes through remodeling of the BAF complex. To elucidate the genomic events that drive phenotypic diversity in SS, we performed RNA and targeted DNA sequencing on 91 tumors from 55 patients. Our results were verified by proteomic analysis, public gene expression cohorts and single-cell RNA sequencing. Transcriptome profiling identified three distinct SS subtypes resemb ...[more]

PMID: 39257029

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