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| Status |
Public on Apr 19, 2024 |
| Title |
Alveolar Soft Part Sarcoma is driven by ASPSCR1::TFE3-dependent and therapeutically targetable transcriptional programs [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy driven by the ASPSCR1::TFE3 fusion, though the mechanisms by which this oncogenic transcriptional regulator drives cancer growth are poorly understood. Here, we characterize 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 including cell proliferation, angiogenesis, and mitochondrial biology. ASPSCR1::TFE3 directly interacts 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, and disruption of Cyclin D1/CDK4 signaling led to loss of ASPS proliferative capacity, which when combined with angiogenesis inhibition halted tumor growth in xenografts. These results define the ASPS oncogenic program, mechanisms by which ASPSCR1::TFE3 controls tumor biology, and identify a strategy for therapeutically targeting tumor cell-intrinsic vulnerabilities.
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| Overall design |
To investigate the transcriptional programs in ASPS, we generated ChIP-seq samples from tumors and preclinical models.
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| Contributor(s) |
Matthew L H |
| 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 |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (17)
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| This SubSeries is part of SuperSeries: |
| GSE235739 |
ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs |
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| Relations |
| BioProject |
PRJNA987535 |
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