RNA sequencing data from STS-109 human undifferentiated pleomorphic sarcoma (UPS) cells deficient in DNMT3A or DNMT3B expression
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ABSTRACT:
PROVIDER: PRJNA822643 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18583900.fastq.gz | Fastqsanger.gz | |||
| SRR18583901.fastq.gz | Fastqsanger.gz | |||
| SRR18583902.fastq.gz | Fastqsanger.gz | |||
| SRR18583903.fastq.gz | Fastqsanger.gz | |||
| SRR18583904.fastq.gz | Fastqsanger.gz |
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Project description:Soft tissue sarcoma diagnostics and prognostics are challenging, particularly in highly malignant and pleomorphic subtypes such as undifferentiated pleomorphic sarcoma (UPS) and leiomyosarcoma (LMS). We applied 32K BAC-arrays and gene expression profiling to 18 extremity soft tissue LMS and 31 extremity soft tissue UPS with the aim to identify molecular subtype signatures and genomic prognostic markers. Both the gains/losses and gene expression signatures revealed striking similarities between UPS and LMS, which were indistinguishable using unsupervised hierarchical cluster analysis and significance analysis for microarrays. Gene expression analysis revealed just 9 genes, among them Tropomyosin beta, that were differentially expressed. Loss of 4q31 (encompassing the SMAD1 locus), loss of 18q22 and tumor necrosis were identified as independent predictors of metastasis in multivariate stepwise Cox regression analysis. Combined analysis applying loss of 4q31 and 18q22 and presence of necrosis improved the area under receiver operating characteristic curve for metastasis prediction from 0.64 to 0.86. The extensive genetic similarities between extremity soft tissue UPS and LMS suggest a shared lineage of these STS subtypes and the new and independent genetic prognosticators identified hold promise for refined prognostic determination in high-grade, genetically complex STS. Genomic DNA was extracted from a total of 49 samples, 31 Undifferentiated pleomorphic Sarcomas and 18 Leiomyosarcomas. The DNA was labeled using Bioprime array CGH labeling kit (Invitrogen). Promega pooled male DNA was used as reference. Labeled DNA was hybridized onto BAC arrays containing ~32 000 BAC clones printed in singlets. BAC arrays were produced at the SWEGENE DNA Microarray Facility at Lund University.
2010-10-08 | E-GEOD-13775 | biostudies-arrayexpress
Project description:Soft tissue sarcoma diagnostics and prognostics are challenging, particularly in highly malignant and pleomorphic subtypes such as undifferentiated pleomorphic sarcoma (UPS) and leiomyosarcoma (LMS). We applied 32K BAC-arrays and gene expression profiling to 18 extremity soft tissue LMS and 31 extremity soft tissue UPS with the aim to identify molecular subtype signatures and genomic prognostic markers. Both the gains/losses and gene expression signatures revealed striking similarities between UPS and LMS, which were indistinguishable using unsupervised hierarchical cluster analysis and significance analysis for microarrays. Gene expression analysis revealed just 9 genes, among them Tropomyosin beta, that were differentially expressed. Loss of 4q31 (encompassing the SMAD1 locus), loss of 18q22 and tumor necrosis were identified as independent predictors of metastasis in multivariate stepwise Cox regression analysis. Combined analysis applying loss of 4q31 and 18q22 and presence of necrosis improved the area under receiver operating characteristic curve for metastasis prediction from 0.64 to 0.86. The extensive genetic similarities between extremity soft tissue UPS and LMS suggest a shared lineage of these STS subtypes and the new and independent genetic prognosticators identified hold promise for refined prognostic determination in high-grade, genetically complex STS.
2009-03-24 | GSE13775 | GEO
Project description:DNA methylation is frequently disrupted in sarcoma but little is known about the specific roles of DNA methyltransferases (DNMTs) in this process. Using an shRNA lentivirus-mediated genetic depletion approach, we found that reduction of DNMT3A or DNMT3B expression potently reduced UPS cell proliferation. Therefore, we performed RNA sequencing to identify global gene expression changes in DNMT3A- or DNMT3B-depleted cells.
2022-10-03 | GSE200026 | GEO
Project description:Transcriptional profiling of leiomyosarcomas (LMS) and undifferentiated pleomorphic sarcomas (UPS) aiming to identify molecular biomarkers. Data were validated using RT-qPCR. To assess the relevance of the gene signature, a meta-analysis was performed using five published studies. SRC protein immunolabeling was performed for 38 UPS and 52 LMS.
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Project description:Undifferentiated pleomorphic sarcoma (UPS) and related tumors are the most common type of soft tissue sarcoma. However, this spectrum of tumors has different etiologies with varying rates of metastasis and survival. Two dermal-based neoplasms in this class of pleomorphic sarcomas, atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS), are challenging to differentiate at initial biopsy but vary significantly in prognosis. We performed single-cell transcriptomics on five AFX and PDS biopsy specimens as well as both single-cell and spatial transcriptomics on one PDS excision specimen to better characterize these tumors. The top differential genes between AFX and PDS were predictive of overall survival in 17 other cancers included in the Human Protein Atlas. Of these genes, COL6A3 and BGN predicted overall survival and metastasis-free survival in independent cohorts of 46 and 38 UPS tumors, respectively. COL6A3 was most predictive of overall survival in UPS patients and outperformed an established sarcoma prognostic gene panel at predicting metastasis in UPS.
2024-11-10 | GSE281529 | GEO
Project description:Undifferentiated pleomorphic sarcoma (UPS) and related tumors are the most common type of soft tissue sarcoma. However, this spectrum of tumors has different etiologies with varying rates of metastasis and survival. Two dermal-based neoplasms in this class of pleomorphic sarcomas, atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS), are challenging to differentiate at initial biopsy but vary significantly in prognosis. We performed single-cell transcriptomics on five AFX and PDS biopsy specimens as well as both single-cell and spatial transcriptomics on one PDS excision specimen to better characterize these tumors. The top differential genes between AFX and PDS were predictive of overall survival in 17 other cancers included in the Human Protein Atlas. Of these genes, COL6A3 and BGN predicted overall survival and metastasis-free survival in independent cohorts of 46 and 38 UPS tumors, respectively. COL6A3 was most predictive of overall survival in UPS patients and outperformed an established sarcoma prognostic gene panel at predicting metastasis in UPS.
2024-11-08 | GSE281096 | GEO
Project description:Although radiotherapy plays a crucial role in treating many cancers, the effect of radiation on tumor evolution remains unclear. We integrated temporal genomic profiling of 120 spatially distinct tumor regions from 20 patients with undifferentiated pleomorphic sarcomas (UPS), longitudinal circulating tumor DNA (ctDNA) analysis, and evolutionary biology computational pipelines to study UPS evolution during tumorigenesis and in response to radiotherapy. Most unirradiated UPS displayed initial linear evolution followed by subsequent branching evolution with distinct mutational processes during early and late development. Using metrics of genetic divergence between regions, we demonstrated evidence of strong selection pressures during UPS development that further increased during radiotherapy. We observed changes in subclone abundance following radiotherapy with subclone contraction tied to alterations in calcium signaling and demonstrated that inhibiting calcium transporters can radiosensitize sarcoma cells. Finally, ctDNA analysis accurately measured subclone abundance and enabled non-invasive monitoring of subclonal changes. These results demonstrate that radiation exerts selective pressures on UPS and suggest that targeting radioresistant subclonal populations could improve outcomes after radiotherapy.
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Project description:Analysis of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma-like tumors from LSL-KrasG12D, p53Fl/Fl mouse model of soft tissue sarcoma.
2009-11-21 | GSE16779 | GEO
Project description:Transcriptional profiling of leiomyosarcomas (LMS) and undifferentiated pleomorphic sarcomas (UPS) aiming to identify molecular biomarkers. Data were validated using RT-qPCR. To assess the relevance of the gene signature, a meta-analysis was performed using five published studies. SRC protein immunolabeling was performed for 38 UPS and 52 LMS. Experiment condition, 22 LMS vs. 22 UPS. Total RNA extracted from tumors was labeled with Cy5, while a custom reference sample (combination of equal amounts of total RNA obtained from 15 different human cell lines) was labeled with Cy3. Samples Cy3 and Cy5 were mixed and hybridized on a two-Color Human GE 4X44K Microarray platform (Agilent Technologies, Palo Alto, CA, USA).
2013-09-15 | E-GEOD-49941 | biostudies-arrayexpress
Project description:Background: Undifferentiated pleomorphic sarcoma (UPS), used to be called malignant fibrous histiocytoma (MFH), is a malignant soft tissue tumor of uncertain origin, and is characterized by morphology. UPS often share similar morphological characters with other sarcomas, especially Leiomyosarcoma. Leiomyosarcoma (LMS) is another malignant soft tissue sarcoma with complex genomic abnormalities, origin from smooth muscle. As a result, development of gene signature and/or biomarkers distinguishing UPS and LMS will definitely help the pathologist to precisely diagnose those patients. However, in the past, UPS was reported to be indistinguishable with LMS by genomic profiles. Methods and Results: In this study, 3’ end RNA Sequencing (3SEQ) was used to expression profile 6 UPS and 99 LMS cases. Overall, UPS was undistinguished with LMS by 3SEQ data, however, when we stratified LMS into three subtypes, UPS was shown to share similar expression pattern with Subtype II LMS, but had distinct molecular expression patterns with Subtype I and Subtype III LMS. Additional Immunohistochemistry staining by using LMS Subtype I and Subtype II markers validated that UPSs were positive for Subtype II marker ARL4C, but negative for Subtype I marker LMOD1. Furthermore, CD4 was shown to be significantly more highly expressed in UPS than LMS in both mRNA and protein levels. Conclusion: This study first reported that UPS shared similar gene expression pattern with subtype II LMS and UPS recapitulated the expression profiles of subtype II LMS.
2015-05-19 | GSE53844 | GEO