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| Status |
Public on Apr 19, 2024 |
| Title |
ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
This SuperSeries is composed of the SubSeries listed below.
Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy driven by the ASPSCR1::TFE3 fusion. A better understanding of the mechanisms by which this oncogenic transcriptional regulator drives cancer growth is needed to help identify potential therapeutic targets. Here, we characterized the transcriptional and chromatin landscapes of ASPS tumors and preclinical models, identifying the essential role of ASPSCR1::TFE3 in tumor cell viability by regulating core transcriptional programs involved in cell proliferation, angiogenesis, and mitochondrial biology. ASPSCR1::TFE3 directly interacted with key epigenetic regulators at enhancers and promoters to support ASPS-associated transcription. Among the effector programs driven by ASPSCR1::TFE3, cell proliferation was driven by high levels of cyclin D1 expression. Disruption of cyclin D1/CDK4 signaling led to loss of ASPS proliferative capacity, and combined inhibition of CDK4/6 and angiogenesis halted tumor growth in xenografts. These results define the ASPS oncogenic program, reveal mechanisms by which ASPSCR1::TFE3 controls tumor biology, and identify a strategy for therapeutically targeting tumor cell-intrinsic vulnerabilities.
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| |
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| Overall design |
Refer to individual Series
|
| |
|
| Citation(s) |
38657118 |
| |
| Submission date |
Jun 26, 2023 |
| Last update date |
Jul 19, 2024 |
| Contact name |
Matthew Hemming |
| E-mail(s) |
matthew.hemming@umassmemorial.org
|
| Organization name |
UMass Medical School
|
| Street address |
364 Plantation Street
|
| City |
Worcester |
| State/province |
MA |
| ZIP/Postal code |
01605 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (62)
|
|
| This SuperSeries is composed of the following SubSeries: |
| GSE235737 |
Alveolar Soft Part Sarcoma is driven by ASPSCR1::TFE3-dependent and therapeutically targetable transcriptional programs [ChIP-Seq] |
| GSE235738 |
Alveolar Soft Part Sarcoma is driven by ASPSCR1::TFE3-dependent and therapeutically targetable transcriptional programs [RNA-Seq] |
| GSE255962 |
Alveolar Soft Part Sarcoma is driven by ASPSCR1::TFE3-dependent and therapeutically targetable transcriptional programs [ATAC-Seq] |
|
| Relations |
| BioProject |
PRJNA987529 |
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