Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dissociation Protocols used for Sarcoma Tissues Bias the Transcriptome observed in Single-cell and Single-nucleus RNA sequencing.

ABSTRACT: To determine whether sarcomas – tumors of mesenchymal origin – are subject to the same technical artifacts, we profiled patient-derived tumor explants (PDXs) propagated from three aggressive subtypes: osteosarcoma, Ewing sarcoma (ES), desmoplastic small round cell tumor (DSRCT). Given the rarity of these sarcoma subtypes, we explored whether single-nuclei RNA-seq from more widely available archival frozen specimens could accurately be identified by gene expression signatures linked to tissue phenotype or pathognomonic fusion proteins.

ORGANISM(S): Homo sapiens

PROVIDER: GSE200529 | GEO | 2023/07/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Proteomic Comparison Of DSRCT, Normal Mesenteric Tissues and ES

Project description:Desmoplastic small round cell tumor (DSRCT) is an aggressive malignancy that occurs predominantly in young adult males and is characterized by abdominopelvic sarcomatosis exhibiting multi-lineage cellular nests of epithelial, muscular, mesenchymal, and neural differentiation admixed with desmoplastic stroma. Prior to the recognition of the disease as a distinct clinical entity, DSRCT was invariably misclassified as poorly differentiated atypical cancer of the testes, ovary, mesentery, or gastrointestinal tract, and the chemotherapies used for those malignancies elicited poor clinical response. As previously reported, a tectonic shift in the treatment of these patients occurred after researchers made two astute observations: 1) DSRCT microscopically resembles other small round “blue cell” sarcoma subtypes (e.g., ES, rhabdomyosarcoma, synovial sarcoma), and 2) DSRCT and ES have the same N-terminal EWSR1 fusion partner. Proteomic analysis using a reverse-phase protein lysate array (RPPA) was used to elucidate biomarkers that distinguish DSRCT from adjacent normal tissue and Ewing sarcoma. This proteomic analysis revealed novel proteins, such as the androgen receptor and Syk, that may be susceptible to drug targeting, as well as oncogenic pathways like Akt-PI3K that are highly expressed in DSRCT.

2020-12-31 | GSE108687 | GEO

Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in Desmoplastic Small Round Cell Tumors [scRNA-Seq]

Project description:Desmoplastic Small Round Cell Tumor (DSRCT) is a rare, aggressive sarcoma driven by the EWSR1-WT1 chimeric transcription factor. Despite this unique oncogenic driver, DSRCT displays a polyphenotypic differentiation of unknown causality. Using single-cell multi-omics on samples from patients, we find that DSRCT tumor cells cluster into consistant subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs.

2024-04-15 | GSE263521 | GEO

Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in Desmoplastic Small Round Cell Tumors [snMultiome]

2024-04-15 | GSE263522 | GEO

RNA-Seq of Primary and Recurrent DSRCT Tumors

Project description:Desmoplastic small round cell tumor (DSRCT) is a rare pediatric cancer caused by the EWSR1-WT1 fusion oncogene. Despite initial response to chemotherapy, DSRCT has a recurrence rate of over 80% leading to poor patient prognosis with a 5-year survival rate of only 15-25%. Owing to the rarity of DSRCT, sample scarcity is a barrier to understanding DSRCT biology and developing effective therapies. Here, we performed RNA-sequencing on a novel pair of primary and recurrent DSRCT tumors harvested from the same patient 5-years apart. To gain insights into gene expression alterations associated with recurrence, we performed pathway analysis on Gene Ontology Biological Processes and KEGG pathways. Upregulated pathways in the recurrent tumor included DNA repair and mRNA splicing related pathways, while downregulated pathways included immune system function and focal adhesion. We further examined the expression of previously identified EWSR1-WT1 regulated targets, a large number of which were enriched in the recurrent tumor. Overall, this study provides novel understanding of DSRCT biology and a new RNA-seq data set to advance future studies.

2023-07-19 | GSE230603 | GEO

Genome-wide AR and H3K27Ac binding profiles in DSRCT cells, xenograft and PDX mouse tumors

Project description:DSRCT is an aggressive, often fatal, sarcoma subtype that usually present in post-pubertal adolescents and young adults. Though the pathognomonic EWSR1-WT1 fusion protein is responsible for tumorigenesis, the androgen receptor (AR) has been suggested as a key contributor to tumor survival and growth. Reverse-phase protein lysate arrays (RPPA) were used to identify new drug targets in DSRCT not present in Ewing sarcoma, a close molecular cousin that shares an EWSR1 N-terminus chimeric partner. Among the 151 proteins analyzed, the AR protein was the most differentially expressed protein, which led to follow-on studies to investigate its role in DSRCT survival and growth in cell lines, xenografts, and patient-derived tumor explants (PDXs), which retain the best fidelity to their human tumor counterparts. Modern-day 2nd-generation AR antagonists were tested for preclinical antitumor activity, in addition to novel AR-directed antisense oligonucleotides that rapidly suppress post-transcriptional activity. Our research demonstrates an important role for the AR in promoting tumor growth and survival in preclinical DSRCT models. Given the widespread availability of safe, orally administered FDA-approved agents used for prostate cancer, such as abiraterone or enzalutamide that potently block AR steroidogenesis or intracellular AR signaling, one could quickly evaluate their effect in DSRCT in phase 2 trials.

2022-06-21 | GSE151380 | GEO

Copy number variation analysis of desmoplastic malignant mesothelioma

Project description:Desmoplastic malignant mesothelioma is a rare tumor. Due to the rarity, genomic profile of desmoplastic malignant mesothelioma is not unveiled. To elucidate genomic profile of desmoplastic malignant mesothelioma, we used illumina infinium omini exomeexpress in an established patient-derived cell line of desmoplastic malignant mesothelioma.

2021-10-18 | GSE185549 | GEO

N3 induced reprogramming and ShWT1 knock-down in DSRCT cell lines

Project description:The object of this study is to identify the molecular signature underlying the therapeutic potential of N3-induced growth arrest in Desmoplastic Small Round Cell Tumor (DSRCT). The molecular hallmark of DSRCT is the EWS-WT1 fusion protein formed by chromosomal translocations found in DSRCT. The N-terminal transactivation domain of EWS is fused to the C-terminal DNA binding domain of WT1, creating an oncogenic transcription factor. We have recently discovered that addition of N3 supplement to growing DSRCT cells leads to a rapid cessation of cell growth.

2022-04-14 | GSE180031 | GEO

The Androgen Receptor: A Therapeutic Target In Desmoplastic Small Round Cell Sarcoma

Project description:Desmoplastic small round cell tumor (DSRCT) is an aggressive, usually incurable sarcoma subtype that predominantly occurs in post-pubertal young males. Recent evidence suggests that the androgen receptor (AR) can promote tumor progression in DSRCTs. However, the mechanism of AR-induced oncogenic stimulation remains undetermined. Herein, we demonstrate that AR-directed antisense oligonucleotides (AR-ASO) block 5-dihydrotestosterone (DHT)-induced DSRCT cell proliferation and reduced xenograft tumor burden. RPPA analysis was performed to elucidate how AR signaling regulates cellular programs. To gain a preliminary understanding of the short-term pharmacodynamic effects of AR suppression, a group of JN-DSRCT xenografts was collected 10 days into their AR-ASO treatment for analysis by RPPA to assess early compensatory pharmacodynamic changes. Its blockade has long been of interest in managing prostate cancer, where a compensatory increase in AKT signaling has been reported following AR inhibition. Therefore, these results collectively validate another proof of concept of AR-based antisense activity in DSRCT and suggest a clinical path forward since the AR-ASO (AZD5312) was safe, and often effective, in PC patients (NCT03300505). Our findings have immediate clinical implications given the widespread availability of FDA-approved androgen-targeted agents used for prostate cancer.

2022-02-28 | GSE178406 | GEO

ena-DATASET-DSRCT-25-02-2018-21:30:33:901-124 - samples

Project description:Desmoplastic small round cell tumor (DSRCT) RNAseq data. 14 tumor samples.

| EGAD00001003980 | EGA

Comprehensive kinase activity assay of desmoplastic malignant mesothelioma

Project description:Desmoplastic malignant mesothelioma is a rare tumor. Due to the rarity, development of new treatment for desmoplastic malignant mesothelioma is difficult. To develop new treatment strategy using existing anti-cancer drugs, kinase activity profiling has not been thoroughly studied. We used PamChip array to identify the peptide profiles of desmoplastic malignant mesothelioma between the patient-derived cell line and the tumor tissue.

2021-10-01 | GSE185107 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data