DataVXAdvanced SciencePaper
journal article·2024-11Open access

Molecular Profiling Defines Three Subtypes of Synovial Sarcoma

Yi Chen, Yanhong Su, Xiaofang Cao, Ioannis Siavelis, Isabelle Rose Leo, Jianming Zeng, Panagiotis Tsagkozis, Asle C. Hesla, Andri Papakonstantinou, Xiao Liu, Wen‐Kuan Huang, Binbin Zhao, Cecilia Haglund, Monika Ehnman, Henrik Johansson, Yingbo Lin, Janne Lehtiö, Yifan Zhang, Olle Larsson, Xuexin Li, Felix Haglund de Flon

Advanced Science· Volume 11· Issue 41
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Source abstract

Abstract

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.
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Research context

OpenAlex topics: Sarcoma Diagnosis and Treatment · Lymphoma Diagnosis and Treatment · Cancer-related molecular mechanisms research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Division of Hematology and Oncology Department of Medicine Columbia Stem Cell Initiative Columbia University Irving Medical Center New York 10032 USA

Department of Genetics and Development Vagelos College of Physicians and Surgeons Columbia University Irving Medical Center New York 10032 USA

Program for Mathematical Genomics Department of Systems Biology Columbia University New York 10032 USA

Department of Oncology‐Pathology Karolinska Institutet Stockholm 17177 Sweden

Science for Life Laboratory Stockholm 17165 Sweden

Faculty of Health Sciences University of Macau Taipa Macau 999078 China

Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm 17176 Sweden

Department of Clinical Orthopedics Karolinska University Hospital Stockholm 17176 Sweden

Department of Breast Cancer Endocrine Tumors and Sarcomas Karolinska University Hospital Stockholm 17176 Sweden

College of Veterinary Medicine Northwest A&F University Yangling Shaanxi 712100 China

Division of Hematology‐Oncology Department of Internal Medicine Chang Gung Memorial Hospital at Linkou Chang Gung University College of Medicine Taoyuan 33305 Taiwan

Department of Clinical Pathology and Cancer Diagnostics Karolinska University Hospital Solna 17176 Sweden

Department of General Surgery The Fourth Affiliated Hospital China Medical University Shenyang 110032 China

Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors Ministry of Education China Medical University Shenyang Liaoning 110122 China

Institute of Health Sciences China Medical University Shenyang Liaoning 110122 China

Department of Physiology and Pharmacology Karolinska Institute Solna Stockholm 17165 Sweden

Funding

Vetenskapsrådet · Cancerfonden · Karolinska Institutet

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