Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA218742 | ENA |
REPOSITORIES: ENA
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Project description:Drug Synergy Screen and Network Modeling in Dedifferentiated Liposarcoma (DDLS) part 2
| PRJNA218741 | ENA
Project description:To define mechanisms that regulate biological behavior in well- and dedifferentiated liposarcoma (WD/DDLS) subsets, we describe an integrative analysis of DNA sequence, copy number and gene expression in 9 paired WDLS and DDLS samples with validation cohorts and in vitro studies. Amplification of 12q13-15 was common to all WDLS; 6q23-25 amplifications were observed 18% of WDLS and were associated with increased TAB2 and higher local recurrence risk versus non-6q-amplified WDLS. TAB2 knockdown decreased MDM2 protein expression and induced markers of cellular senescence in 6q23-25-amplified WDLS cells but not in non-amplified WDLS of amplified DDLS cells. Amplification of 6q23-25 was not associated with DDLS recurrence risk or progression from WDLS to DDLS. Instead, pathogenic ATRX mutations, recurrent losses in 13q and gains in 8q12-21 accompanied dedifferentiation. Downregulation of the 13q-encoded genes MYCBP2 and IRS2 was observed in DDLS versus WDLS; in vitro, these genes were essential for WDLS cell differentiation. Taken together, this study defines a copy number-driven model of liposarcoma initiation, progression, and differentiation.
2026-08-04 | GSE244163 | GEO
Project description:To define mechanisms that regulate biological behavior in well- and dedifferentiated liposarcoma (WD/DDLS) subsets, we describe an integrative analysis of DNA sequence, copy number and gene expression in 9 paired WDLS and DDLS samples with validation cohorts and in vitro studies. Amplification of 12q13-15 was common to all WDLS; 6q23-25 amplifications were observed 18% of WDLS and were associated with increased TAB2 and higher local recurrence risk versus non-6q-amplified WDLS. TAB2 knockdown decreased MDM2 protein expression and induced markers of cellular senescence in 6q23-25-amplified WDLS cells but not in non-amplified WDLS of amplified DDLS cells. Amplification of 6q23-25 was not associated with DDLS recurrence risk or progression from WDLS to DDLS. Instead, pathogenic ATRX mutations, recurrent losses in 13q and gains in 8q12-21 accompanied dedifferentiation. Downregulation of the 13q-encoded genes MYCBP2 and IRS2 was observed in DDLS versus WDLS; in vitro, these genes were essential for WDLS cell differentiation. Taken together, this study defines a copy number-driven model of liposarcoma initiation, progression, and differentiation. Array comparative genomic hybridization (aCGH) was performed using Agilent 244K or 1M arrays and analyzed using the RAE pipeline as previously reported (Barretina J, et. al, Nat Genet. 2010;42(8):715-21, PMC2911503 and Crago AM, et. al, Clin Cancer Res. 2012;18(5):1334-40, PMC3294014)
2026-08-04 | GSE336156 | GEO
Project description:Well-differentiated and dedifferentiated liposarcoma (WD/DDLS), myxofibrosarcoma (MFS), and undifferentiated pleomorphic sarcoma (UPS) are the most common types of genetically complex sarcoma. There is an urgent need to develop effective targeted therapy for the over 50% of patients who eventually die of disease. Despite their genetic complexity, all four sarcoma types rely on the oncogenic translation of Hippo pathway proteins, which requires the RNA helicase eIF4A (DDX2). Pharmacological inhibition of eIF4A using CR-1-31B effectively suppressed tumor growth and induced apoptosis in DDLS, MFS, and UPS patient-derived cell lines and mouse xenografts. Transcriptome-scale ribosome footprinting identified eIF4A-dependent mRNAs in DDLS, MFS, and UPS cell lines. These include Hippo pathway effectors such as YAP1, WWTR1 (TAZ), and TEAD1. Combined knockdown of YAP and TAZ induced apoptosis in DDLS, MFS, and UPS cell lines, implicating them as critical targets. Hence, DDLS, MFS, and UPS rely on the eIF4A-dependent and CR-1-31B-sensitive translation of Hippo pathway oncogenes such as YAP, TAZ, and TEAD. eIF4A thus represents a new, promising therapeutic target for these incurable forms of soft tissue sarcoma.
2025-12-14 | GSE227676 | GEO
Project description:Analysis of gene expression levels in two DDLS tumor-derived cell lines DDLS8817 and LPS141 growing in culture in basal conditions The goal of this gene transcript study was to determine the expression level of genes used in signaling network modeling in DDLS
2013-09-24 | GSE50749 | GEO
Project description:Analysis of DNA copy number variations in two DDLS tumor-derived cell lines DDLS8817 and LPS141 growing in culture in basal conditions The goal of this DNA copy number analysis was to determine if genes used in signaling network modeling in DDLS were amplified or deleted
2013-09-24 | GSE50750 | GEO
Project description:Analysis of DNA copy number variations in two DDLS tumor-derived cell lines DDLS8817 and LPS141 growing in culture in basal conditions The goal of this DNA copy number analysis was to determine if genes used in signaling network modeling in DDLS were amplified or deleted Genomic DNA was isolated from asynchronously growing DDLS8817 and LPS141 cultures growing in basal conditions using the Qiagen DNAy kit.
2013-09-24 | E-GEOD-50750 | biostudies-arrayexpress
Project description:Analysis of gene expression levels in two DDLS tumor-derived cell lines DDLS8817 and LPS141 growing in culture in basal conditions The goal of this gene transcript study was to determine the expression level of genes used in signaling network modeling in DDLS RNA was isolated from asynchronously growing DDLS8817 and LPS141 cultures growing in basal conditions using the Qiagen RNEasy kit. Three replicates of each cell line
2013-09-24 | E-GEOD-50749 | biostudies-arrayexpress
Project description:Background: Liposarcoma constitute about 13% of all soft tissue sarcoma and are associated with a high risk of metastases. As the preoperative differentiation between benign and malign lipomatous tumors is restricted to magnetic resonance imaging, computed tomography and biopsy, we performed a miRNA array to distinguish liposarcoma patients from healthy controls and lipoma patients. Workflow: Blood samples of patients with dedifferentiated liposarcoma, healthy controls and lipoma patients were collected. Whole blood RNA was extracted and samples of patients with dedifferentiated liposarcoma (n=6) and of healthy donors (n=4) were analyzed using an Affymetrix GeneChip miRNA Array v. 4.0. qRT-PCR was carried out to confirm the most differentially expressed miRNA; being further analyzed in an independent cohort of healthy controls as well as in lipoma patients. Results: As shown by the microarray, two miRNAs (miR-4668-5p and miR-3613-3p) were shown to be significantly upregulated (fold change: >2.5; p<0.05) in patients with dedifferentiated liposarcoma (n=6) as compared to healthy controls (n=4). miR-4668-5p was further validated by qRT-PCR to be significantly upregulated in liposarcoma patients compared to an independent cohort of healthy controls (n=3) and lipoma patients (n=6). Conclusion: We identified a specific whole blood miRNA (miR-4668-5p) that may serve to distinguish between lipoma and liosarcoma patients, thus potentially serving as a specific biomarker for dedifferentiated liposarcoma.
2018-06-01 | E-MTAB-5126 | biostudies-arrayexpress