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Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE276074 | GEO | 2024/11/06

REPOSITORIES: GEO

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Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis.

Project description: Not available

| S-EPMC12436642 | biostudies-literature

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

Project description: Not available

| S-EPMC11463515 | biostudies-literature

Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis [CRISPR Screening]

Project description:Synovial sarcoma (SySa) is an aggressive soft tissue sarcoma with an urgent need to develop targeted therapies. Here, we exploited specific vulnerabilities created by transcriptional rewiring by the fusion protein SS18::SSX, the sole oncogenic driver in SySa. To uncover genes that are selectively essential for the fitness of SySa cells compared to other tumor cell lines, we mined the Cancer-Dependency-Map data. Targeted CRISPR library screening of SySa-selective candidates revealed that the small ubiquitin-like modifier 2 (SUMO2) constituted one of the strongest dependencies both in vitro and in vivo. TAK-981, a clinical-stage small-molecule SUMO2 inhibitor potently suppressed growth and colony-forming ability. Transcriptomic profiling showed that SUMO2 inhibition elicited a profound reversal of the gene expression program orchestrated by SS18::SSX fusion. Further, genetic depletion or SUMO2 inhibition reduced global expression levels and chromatin occupancy of the SS18::SSX fusion protein with a concomitant reduction in histone 2A lysine 119 ubiquitination (H2AK119ub), an epigenetic mark facilitating SySa pathogenesis. Taken together, our study identifies SUMO2 as a novel, selective vulnerability in synovial sarcoma, suggesting new avenues for targeted treatment of soft tissue tumors.

2024-11-06 | GSE274712 | GEO

Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis [ChIP-seq]

2024-11-06 | GSE276068 | GEO

Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis [RNA-seq]

2024-11-06 | GSE276073 | GEO

Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis [CUT&RUN]

2024-11-06 | GSE276071 | GEO

Targeting SUMO2 Reverses Aberrant Epigenetic Rewiring Driven by SS18::SSX Fusion Oncoproteins and Impairs Sarcomagenesis

Project description: Not available

| S-SCDT-10_1038-S44318-025-00526-W | biostudies-other

Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis

Project description:Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis

| PRJNA1154630 | ENA

Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis [ChIP-seq]

Project description:Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis [ChIP-seq]

| PRJNA1154633 | ENA

Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis [RNA-seq]

Project description:Targeting SUMO2 reverses aberrant epigenetic rewiring driven by SS18::SSX fusion oncoproteins and impairs sarcomagenesis [RNA-seq]

| PRJNA1154640 | ENA

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