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Series GSE235738 Query DataSets for GSE235738
Status Public on Apr 19, 2024
Title Alveolar Soft Part Sarcoma is driven by ASPSCR1::TFE3-dependent and therapeutically targetable transcriptional programs [RNA-Seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
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.
 
Overall design To investigate the transcriptional programs in ASPS, we generated RNA-seq samples from tumors and preclinical models. RNA-seq was performed on cell cultures and xenografts following treatment with palbociclib.
 
Contributor(s) Matthew L H
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Submission date Jun 26, 2023
Last update date Apr 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 (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (35)
GSM7508724 ASPS_PDX_F0
GSM7508725 ASPS_PDX_F4
GSM7508726 ASPS-1
This SubSeries is part of SuperSeries:
GSE235739 ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs
Relations
BioProject PRJNA987537

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE235738_ASPS_RNAseq.txt.gz 2.1 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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