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. 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 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.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Molecular Profiling Defines Three Subtypes of Synovial Sarcoma ; day:10 ; month:09 ; year:2024 ; extent:18
Advanced science ; (10.09.2024) (gesamt 18)
- Creator
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Chen, Yi
Su, Yanhong
Cao, Xiaofang
Siavelis, Ioannis
Leo, Isabelle Rose
Zeng, Jianming
Tsagkozis, Panagiotis
Hesla, Asle C.
Papakonstantinou, Andri
Liu, Xiao
Huang, Wen‐Kuan
Zhao, Binbin
Haglund, Cecilia
Ehnman, Monika
Johansson, Henrik
Lin, Yingbo
Lehtiö, Janne
Zhang, Yifan
Larsson, Olle
Li, Xuexin
de Flon, Felix Haglund
- DOI
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10.1002/advs.202404510
- URN
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urn:nbn:de:101:1-2409111411481.149395415084
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:32 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Chen, Yi
- Su, Yanhong
- Cao, Xiaofang
- Siavelis, Ioannis
- Leo, Isabelle Rose
- Zeng, Jianming
- Tsagkozis, Panagiotis
- Hesla, Asle C.
- Papakonstantinou, Andri
- Liu, Xiao
- Huang, Wen‐Kuan
- Zhao, Binbin
- Haglund, Cecilia
- Ehnman, Monika
- Johansson, Henrik
- Lin, Yingbo
- Lehtiö, Janne
- Zhang, Yifan
- Larsson, Olle
- Li, Xuexin
- de Flon, Felix Haglund
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