Comprehensive gene expression analysis identifies a unique molecular profile and macrophage infiltration in undifferentiated uterine sarcomas [expression]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE85383 | GEO | 2017/08/01
SECONDARY ACCESSION(S): PRJNA338308
REPOSITORIES: GEO
Similar Datasets
Project description:Sarcomas originating from the endometrial stroma include low- and high-grade endometrial stromal sarcomas (ESS) that are associated with specific translocations, and highly malignant undifferentiated uterine sarcomas (UUS). UUS is considered a poorly defined group of tumors and is often seen as a “diagnosis of exclusion” after ESS and leiomyosarcoma (LMS) have been ruled out. Using aCGH, we showed that UUS more complex genomic aberrations that low- and high-grade ESS.
2017-08-01 | GSE85382 | GEO
Project description:Based on the transcriptome analysis of 555 sarcomas, we identified a group of tightly clustered leiomyosarcomas (LMS) due to their gene expression homogeneity. We named them “hLMS” and the other LMS “oLMS”. We derived a transcriptional signature able to identify each group and used it to classify patients from two independent cohorts. In all cohorts, hLMS were preferentially carried by women, located in the internal trunk, highly differentiated, and similarly altered at the genomic level. Based on integrative bioinformatic analysis, we show that hLMS originate from vascular smooth muscle cells presenting both contractile and synthetic characteristics, while oLMS could derive from fibroblasts. We found strong MYOCD expression to be an hLMS-specific driver and show that the MYOCD/SRF axis is essential only for hLMS survival. Identification of hLMS could become standard clinical practice, leading to the development of specific effective treatments with MYOCD/SRF inhibitors. These 87 samples from leiomyosarcoma primary tumors were analysed on Affymetrix and Agilent platforms and both datasets were used to define genes with consistent expression between the platforms. These genes were then selected in other datasets from the two plaforms before combination and normalization.
2022-12-31 | GSE159847 | GEO
Project description:Endometrial stromal sarcomas (ESSs) are a genetically heterogeneous group of rare uterine neoplasms that are frequently driven by recurrent gene rearrangements. In conventional low-grade ESSs, JAZF1-SUZ12, PHF1-JAZF1, EPC1-PHF1 and MEAF6-PHF1 chimeric fusions have been reported in >50% of cases. The recently described t(10;17)(q22;p13) translocation yields YWHAE-FAM22A/B chimeric proteins that are associated with histologically high-grade and clinically more aggressive ESS. Integrating whole-transcriptome paired-end RNA sequencing with fluorescence in situ hybridization (FISH) and conventional cytogenetics, we identified MBTD1 (Malignant Brain Tumor Domain-containing 1) and CXorf67 (Chromosome X open reading frame 67) as the genes involved in the novel reciprocal t(X;17)(p11.2;q21.33) translocation in two independent low-grade ESS of classical histology. The presence of the MBTD1-CXorf67 fusion transcript was validated in both cases using RT-PCR followed by Sanger sequencing. A specific FISH assay to be used on paraffin tissues was developed to detect the novel t(X;17) translocation, and resulted in identification of an additional low-grade ESS case positive for the MBTD1-CXorf67 fusion among 14 uterine stromal tumours [9 ESSs and 5 undifferentiated endometrial sarcomas (UESs)] that were negative for JAZF1 and YWHAE rearrangements. Gene expression profiles of 3 ESSs with YWHAE- and 4 classical ESSs with JAZF1-rearrangements, and 4 UESs without known gene rearrangements, indicated clustering of tumours with MBTD1-CXorf67 fusion together with low-grade JAZF1-associated ESSs. The chimeric MBTD1-CXorf67 fusion identifies yet another cytogenetically distinct subgroup of low-grade ESS and offers the opportunity to shed light on the functions of two poorly characterized genes. Total RNA was extracted from 11 frozen tumor samples from 4 low-grade ESS cases, 4 UES cases and 3 high-grade ESS cases; Agilent One-Color technology.
2015-03-31 | E-GEOD-45783 | biostudies-arrayexpress
Project description:Endometrial stromal sarcomas (ESSs) are a genetically heterogeneous group of rare uterine neoplasms that are frequently driven by recurrent gene rearrangements. In conventional low-grade ESSs, JAZF1-SUZ12, PHF1-JAZF1, EPC1-PHF1 and MEAF6-PHF1 chimeric fusions have been reported in > 50% of cases. The recently described t(10;17)(q22;p13) translocation yields YWHAE-FAM22A/B chimeric proteins that are associated with histologically high-grade and clinically more aggressive ESS. Integrating whole-transcriptome paired-end RNA sequencing with fluorescence in situ hybridization (FISH) and conventional cytogenetics, we identified MBTD1 (Malignant Brain Tumor Domain-containing 1) and CXorf67 (Chromosome X open reading frame 67) as the genes involved in the novel reciprocal t(X;17)(p11.2;q21.33) translocation in two independent low-grade ESS of classical histology. The presence of the MBTD1-CXorf67 fusion transcript was validated in both cases using RT-PCR followed by Sanger sequencing. A specific FISH assay to be used on paraffin tissues was developed to detect the novel t(X;17) translocation, and resulted in identification of an additional low-grade ESS case positive for the MBTD1-CXorf67 fusion among 14 uterine stromal tumours [9 ESSs and 5 undifferentiated endometrial sarcomas (UESs)] that were negative for JAZF1 and YWHAE rearrangements. Gene expression profiles of 3 ESSs with YWHAE- and 4 classical ESSs with JAZF1-rearrangements, and 4 UESs without known gene rearrangements, indicated clustering of tumours with MBTD1-CXorf67 fusion together with low-grade JAZF1-associated ESSs. The chimeric MBTD1-CXorf67 fusion identifies yet another cytogenetically distinct subgroup of low-grade ESS and offers the opportunity to shed light on the functions of two poorly characterized genes. Genomic DNA extracted from 2 low-grade ESS frozen tumor samples; Agilent CGH+SNP 4x180K array. Reference female DNA supplied with the SureTag Complete DNA Labeling Kit was used for the aCGH experiments.
2015-03-31 | E-GEOD-46284 | biostudies-arrayexpress
Project description:Leiomyosarcoma (LMS) is a malignant neoplasm with smooth muscle differentiation, and there are three molecular subtypes of LMS which have been defined previously by our lab. To further validate these subtypes and identify potential therapeutic targets in each subtype, we profiled the LMS cases from each subtype with RNA-Seq technology.
2015-12-25 | GSE62544 | GEO
Project description:Microarray analysis revealed differential gene expression patterns of rhabdomyosarcoma (A-204), leiomyosarcoma (SK-LMS-1) and epithelioid cell sarcoma (VA-ES-BJ) cells treated with TRAIL and/or taurolidine. To explore new therapeutic options in the treatment of sarcomas, we tested the antibiotic taurolidine (TRD) on A-204, SK-LMS-1 and VA-ES-BJ carcinoma cell lines alone and in combination with rhTRAIL (TNF related apoptosis-inducing ligand). Gene expression was analysed by RNA microarray.
2013-03-17 | GSE36572 | 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.
2013-09-15 | GSE49941 | GEO
Project description:Microarray analysis revealed differential gene expression patterns of rhabdomyosarcoma (A-204), leiomyosarcoma (SK-LMS-1) and epithelioid cell sarcoma (VA-ES-BJ) cells treated with TRAIL and/or taurolidine. To explore new therapeutic options in the treatment of sarcomas, we tested the antibiotic taurolidine (TRD) on A-204, SK-LMS-1 and VA-ES-BJ carcinoma cell lines alone and in combination with rhTRAIL (TNF related apoptosis-inducing ligand). Gene expression was analysed by RNA microarray. Cell lines were treated with Taurolidine, Trail and a combination of both and compaired to untreated cells
2013-03-17 | E-GEOD-36572 | 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. In this study, 3’ end RNA Sequencing (3SEQ) was used to expression profile 6 UPS and 99 LMS cases. In order to explore the molecular differences between UPS and LMS, We analyzed the expression data by SAMseq to identify the genes which were significantly differently expressed between UPS and LMS, between UPS and each LMS subtype.
2015-05-19 | E-GEOD-53844 | 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