Synovial sarcoma with prominent myxoid stroma and negative epithelial markers
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE324018 | GEO | 2026/04/03
REPOSITORIES: GEO
Similar Datasets
Project description:Synovial sarcoma with prominent myxoid stroma and negative epithelial markers
| PRJNA1432983 | ENA
Project description:MicroRNAs (miRNAs) are non-coding small RNAs that function as an endogenous regulator of gene expression. Their dysregulation has been implicated in the development of several cancers. However, the status of miRNA in soft tissue sarcomas has not yet been thoroughly investigated. This study examined the global miRNA expression in synovial sarcoma and compared the results to those in another translocation-associated sarcoma, the Ewing family of tumors, and in normal skeletal muscle. The 3D-Gene miRNA microarray platform (Toray, Kamakura, Japan) and unsupervised hierarchical clustering revealed a distinct expression pattern of miRNAs in synovial sarcoma from Ewing tumors and skeletal muscle. Thirty-five of the more than 700 miRNAs analyzed were differentially expressed in synovial sarcomas in comparison to other tissue types. There were 21 significantly up-regulated miRNAs, including some miRNAs, such as let-7e, miR-99b and miR-125a-3p, clustered within the same chromosomal loci. Quantitative reverse transcription-polymerase chain reaction also demonstrated that these miRNAs were over-expressed in synovial sarcomas. The down-regulation of let-7e and miR-99b by anti-miR miRNA inhibitors resulted in the suppression of the proliferation of synovial sarcoma cells, and modulated the expression of their putative targets, HMGA2 and SMARCA5, suggesting that these molecules have a potential oncogenic role. The unique miRNA expression pattern including the over-expressed miRNA clusters in synovial sarcoma warrants further investigation in order to develop a better understanding of the oncogenic mechanisms and future therapeutic strategies for synovial sarcoma. Ten synovial sarcomas, five Ewing tumors and five normal skeletal muscle specimens are analyzed.
2010-10-21 | E-GEOD-18546 | biostudies-arrayexpress
Project description:Synovial sarcomas account for approximately 10% of all soft-tissue tumors and occur most frequently in young adults. A specific translocation in this sarcoma induces fusion of the SYT gene on chromosome 18 to the SSX genes on chromosome X, leading to proliferation of the tumor cells. The need for non-invasive biomarkers indicating recurrence and activity of this disease has sparked research into short non-coding RNA known as microRNA (miRNA). Patients and Methods: Serum samples of patients with active synovial sarcoma, healthy donors and leiomyosarcoma patients were collected. Cell-free serum was obtained by differential centrifugation steps and analyzed using an Affymetrix GeneChip miRNA Array v. 4.0. qRT-PCR was carried out to confirm a panel of miRNAs which where differentially expressed in the miRNA array.
2018-09-19 | E-MTAB-3888 | biostudies-arrayexpress
Project description:Several variant Polycomb Repressive complexes 1 (vPRC1s) co-exist to robustly deposit mono ubiquitination on histone H2A (H2AK119ub1). Their interconnected roles and specific tasks across normal and disease cellular states remain unclear. In synovial sarcoma (SS), a soft tissue tumor driven by the oncogenic fusion protein, SS18::SSX, the SSX tail exhibits a high affinity to H2AK119ub1 marked genomic regions. This mechanism is crucial to sequester the mSWI/SNF complex to PRC1 targets and results in their aberrant expression. We previously showed that PRC1.1 is responsible for H2AK119ub1 deposition in SS and is therefore required for SS18::SSX occupancy. Here, we investigated the role of PRC1 variants in synovial sarcoma.
2025-03-17 | GSE291441 | GEO
Project description:MicroRNAs (miRNAs) are non-coding small RNAs that function as an endogenous regulator of gene expression. Their dysregulation has been implicated in the development of several cancers. However, the status of miRNA in soft tissue sarcomas has not yet been thoroughly investigated. This study examined the global miRNA expression in synovial sarcoma and compared the results to those in another translocation-associated sarcoma, the Ewing family of tumors, and in normal skeletal muscle. The 3D-Gene miRNA microarray platform (Toray, Kamakura, Japan) and unsupervised hierarchical clustering revealed a distinct expression pattern of miRNAs in synovial sarcoma from Ewing tumors and skeletal muscle. Thirty-five of the more than 700 miRNAs analyzed were differentially expressed in synovial sarcomas in comparison to other tissue types. There were 21 significantly up-regulated miRNAs, including some miRNAs, such as let-7e, miR-99b and miR-125a-3p, clustered within the same chromosomal loci. Quantitative reverse transcription-polymerase chain reaction also demonstrated that these miRNAs were over-expressed in synovial sarcomas. The down-regulation of let-7e and miR-99b by anti-miR miRNA inhibitors resulted in the suppression of the proliferation of synovial sarcoma cells, and modulated the expression of their putative targets, HMGA2 and SMARCA5, suggesting that these molecules have a potential oncogenic role. The unique miRNA expression pattern including the over-expressed miRNA clusters in synovial sarcoma warrants further investigation in order to develop a better understanding of the oncogenic mechanisms and future therapeutic strategies for synovial sarcoma.
2010-10-21 | GSE18546 | GEO
Project description:Synovial sarcoma is an aggressive soft tissue cancer driven by the chimeric SS18::SSX fusion oncoprotein, which disrupts chromatin remodeling by combining two antagonistic transcriptional regulators. SS18 participates in BAF complexes that open chromatin, while the SSX genes are cancer-testis antigens that interface with chromatin decorated with monoubiquitinated histone H2A placed by Polycomb repressive complexes (PRCs) activity. Because KDM2B brings PRC to unmethylated CpG islands, it is plausible that methylation directly determines the distribution of SS18::SSX to target loci. Given that synovial sarcoma is also characterized by a peculiarly low DNA hypomethylation profile, we hypothesized that further disturbance of DNA methylation would have a negative impact on synovial sarcoma growth. DNMT1 disruption by CRISPR/Cas9 targeting or pharmacologic inhibition with cytidine analogs 5-aza-2ʹ-deoxycytidine (decitabine) and 5-azacytidine led to decreased genome-wide methylation, redistribution of SS18::SSX, and altered gene expression profiles, most prominently including upregulation of tumor suppressor genes, immune-related genes, and mesenchymal differentiation-related genes. These drugs suppressed growth of synovial sarcoma cell lines and drove cytoreduction in mouse genetic models. DNMT1 inhibitors, already approved for treating myelodysplastic syndromes, warrant further clinical investigation for synovial sarcoma as repurposed, targeted treatments exploiting a vulnerability in the intrinsic biology of this cancer.
2025-04-18 | GSE292622 | GEO
Project description:Synovial sarcoma is a deadly malignancy of soft-tissue with a predilection for adolescents and young adults that consistently associates with a t(X;18) chromosomal translocation and expression of the resultant fusion oncoprotein SS18::SSX. Here, the dependency on MDM2 that has been observed in multiple synovial sarcoma cell lines is presented. Very few synovial sarcomas in humans demonstrate TP53 mutation or loss, CDKN2A loss, or MDM2 gains, each common among other sarcoma types. Silencing of homologous Trp53 in a mouse model of SS18::SSX-expression-induced sarcomagenesis leads to a slightly reduced latency to tumorigenesis, but no increase in de-differentiated phenotypes, or nuclear pleiomorphism. Transcriptome analysis revealed minimal change in p53 target gene expression, suggesting that expression of the fusion alone was sufficient to impact these. Treatment of mice with the MDM2-p53-intereaction inhibitor, HDM201, was modestly successful at slowing tumor growth, alone. Combined treatment with HDM201 and the HDAC inhibitor panobinostat, known to be capable of derepressing Cdkn2a expression, synergized to curtail synovial sarcoma development.
2026-04-01 | GSE315379 | GEO
Project description:Synovial sarcoma (SyS) is an aggressive soft-tissue malignancy that is characterized by a pathognomonic t(X;18)(p11.2;q11.2) translocation, which produces the fusion oncogene named SS18::SSX. Despite recent advancements in our understanding of synovial sarcoma biology, the cell-of-origin remains undefined. Here we employ a mesenchymal stromal cell (MSC) specific CreERT2 line to express SS18::SSX in fibroblasts and related cell types, resulting in 100% penetrant synovial sarcoma development in mice, with a median latency period of 16.2 ± 2.8 weeks. Murine tumours exhibit high concordance with human synovial sarcoma subtypes at the histological and molecular levels1. Genetic refinement of the cell-of-origin reveal that synovial sarcomas derive from a rare Hic1+ Pdgfra+ Lgr5+ fibroblastic population. Furthermore, comparative transcriptomic analysis reveals the acquisition of a transformed phenotype initiated by the loss of a mature fibroblastic profile and subsequent unmasking of an epigenetically embedded embryonic MSC program. Adult and embryonic MSCs exhibite overlapping H2AK119ub and H3K4me3/H3K27me3 (bivalent) histone marks, while SS18::SSX-mediated transformation culminates in the widespread loss of H3K27me3 at these genes and their consequent transcription. Collectively, these studies define a rare MSC context, conducive for SS18::SSX-mediated transformation, and demonstrate that SyS tumorigenesis involves the induction and maintenance of an embryonic-like MSC phenotype.
2025-09-11 | GSE213265 | GEO
Project description:Synovial sarcoma (SyS) is an aggressive soft-tissue malignancy that is characterized by a pathognomonic t(X;18)(p11.2;q11.2) translocation, which produces the fusion oncogene named SS18::SSX. Despite recent advancements in our understanding of synovial sarcoma biology, the cell-of-origin remains undefined. Here we employ a mesenchymal stromal cell (MSC) specific CreERT2 line to express SS18::SSX in fibroblasts and related cell types, resulting in 100% penetrant synovial sarcoma development in mice, with a median latency period of 16.2 ± 2.8 weeks. Murine tumours exhibit high concordance with human synovial sarcoma subtypes at the histological and molecular levels1. Genetic refinement of the cell-of-origin reveal that synovial sarcomas derive from a rare Hic1+ Pdgfra+ Lgr5+ fibroblastic population. Furthermore, comparative transcriptomic analysis reveals the acquisition of a transformed phenotype initiated by the loss of a mature fibroblastic profile and subsequent unmasking of an epigenetically embedded embryonic MSC program. Adult and embryonic MSCs exhibite overlapping H2AK119ub and H3K4me3/H3K27me3 (bivalent) histone marks, while SS18::SSX-mediated transformation culminates in the widespread loss of H3K27me3 at these genes and their consequent transcription. Collectively, these studies define a rare MSC context, conducive for SS18::SSX-mediated transformation, and demonstrate that SyS tumorigenesis involves the induction and maintenance of an embryonic-like MSC phenotype.
2025-09-11 | GSE216769 | GEO
Project description:Synovial sarcomas account for approximately 10% of all soft-tissue tumors and occur most frequently in young adults. A specific translocation in this sarcoma induces fusion of the SYT gene on chromosome 18 to the SSX genes on chromosome X, leading to proliferation of the tumor cells. The need for non-invasive biomarkers indicating recurrence and activity of this disease has sparked research into short non-coding RNA known as microRNA (miRNA). Patients and Methods: Blood samples of patients with active synovial sarcoma and of healthy donors were collected. Whole blood RNA was extracted and analyzed using an Affymetrix GeneChip miRNA Array v. 4.0. Results: Hierarchical clustering of all covered human mature miRNAs and human pre-miRNAs separated sarcoma samples from control samples. Following hierarchical clustering, the array results were narrowed own to deregulated miRNAs with a fold change > |3.0|, a p-value <0.005, a q-value (FDR-corrected p-value) <0.2 and a similar deregulation of related miRNAs with the same base sequence throughout the array. Unsupervised hierarchical clustering of the panel of miRNAs that met these criteria could again separate sarcoma patients from healthy controls. Conclusion: Our results have identified a specific whole blood miRNA signature that may serve as an independent biomarker for the diagnosis of local recurrence or distant metastasis of synovial sarcoma.
2015-08-03 | E-MTAB-3273 | biostudies-arrayexpress