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SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis

ABSTRACT: SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis

PROVIDER: PRJNA1154630 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30223780_1.fastq.gz	Fastqsanger.gz
	SRR30223780_2.fastq.gz	Fastqsanger.gz
	SRR30223781_1.fastq.gz	Fastqsanger.gz
	SRR30223781_2.fastq.gz	Fastqsanger.gz
	SRR30223782_1.fastq.gz	Fastqsanger.gz

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SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis [RNA-seq]

Project description:SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis [RNA-seq]

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SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis [CRISPR Screening]

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SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis [CUT&RUN]

Project description:SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis [CUT&RUN]

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SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis [ChIP-seq]

Project description:SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis [ChIP-seq]

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SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis [CRISPR Screening]

Project description:Synovial Sarcoma (SySa) is an aggressive soft tissue sarcoma that accounts for 5 – 10% of all soft tissue sarcomas. Current treatment involves radiation and radical surgery including limb amputation, highlighting the urgent need to develop targeted therapies. We reasoned that transcriptional rewiring by the fusion protein SS18-SSX, the sole oncogenic driver in SySa, creates specific vulnerabilities that can be exploited for treatment. To uncover genes that are selectively essential for SySa, we mined the Dependency Maps (Depmap) database to identify genes that specifically impact the fitness of SySa compared to other tumor cell lines. Targeted CRISPR library screening of select SySa-selective candidates revealed that the small ubiquitin-like modifier 2 (SUMO2) was one of the strongest dependencies both in vitro as well as in vivo. TAK-981, a clinical-stage small molecule SUMO2 inhibitor potently inhibited growth, colony-forming ability, and spheroid formation of SySa cell lines. Strikingly, transcriptomic studies showed that TAK-981 treatment elicited a profound reversal of a gene expression program orchestrated by SS18-SSX fusions. Of note, genetic or pharmacological SUMO2 inhibition reduced global and chromatin levels of the SS18-SSX fusion protein with a concomitant reduction in histone 2A lysine 119 ubiquitination (H2AK119ub), an epigenetic mark that is enhanced by the SySa fusions and plays an important role in SySa pathogenesis. Taken together, our studies identify SUMO2 as a novel, selective vulnerability in SySa. Since SUMO2 inhibitors are currently in Phase 1/2 clinical trials for human cancer, our findings present a novel potential avenue for targeted treatment of synovial sarcoma.

2024-11-06 | GSE274712 | GEO

SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis [RNA-seq]

2024-11-06 | GSE276073 | GEO

SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis [CUT&RUN]

2024-11-06 | GSE276071 | GEO

SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis [ChIP-seq]

2024-11-06 | GSE276068 | GEO

SUMO2 Inhibition Reverses Aberrant Epigenetic Rewiring Driven by Synovial Sarcoma Fusion Oncoproteins and Impairs Sarcomagenesis

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-11-06 | GSE276074 | GEO

Expression following beta-catenin stabilization in synovial sarcomagenesis

Project description:Synovial sarcoma is a deadly soft-tissue malignancy with a predilection for adolescents and young adults. Mice recapitulate synovial sarcomagenesis from expression of SS18-SSX2 in certain cells. Concomitant expression of a stabilized form of beta-catenin enhances synovial sarcomagenesis and expands the potential cells of origin.

2015-11-04 | GSE47388 | GEO

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