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Expression data from 87 complex sarcomas

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE159847 | GEO | 2022/12/31

REPOSITORIES: GEO

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miRNA expression data from 39 leiomyosarcomas [miRNA-seq]

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. Particularly, miRNA from 39 leiomyosarcomas (LMS) classified as homogeneous and other LMS according to a mRNA transcriptional signature were sequenced, mapped to mature miRNA sequences and analysed in order to evaluate miRNA impact on LMS biology and oncology. 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.

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Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma (Expression)

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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.

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Transcriptional Profiling of Leiomyosarcoma Cell Lines

Project description:Leiomyosarcoma (LMS) is a mesenchymal neoplasm with complex copy number alterations and characteristic loss of tumor suppressor genes without known recurrent activating oncogenic mutations. Clinical management of advanced LMS relies on cytotoxic chemotherapy and complementary palliative approaches, and research efforts to date have had limited success identifying clinically actionable biomarkers or targeted therapeutic vulnerabilities. To explore the distinctive biological underpinning of LMS, we evaluated gene expression patterns of LMS cell lines and correlated results with primary tumor samples.

2020-01-22 | GSE143968 | GEO

Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma (Expression)

Project description:Global gene expression analysis of inflammatory leiomyosarcoma (ILMS) and conventional leiomyosarcoma (LMS). RNA was extracted from frozen tumor biopsies (3 ILMS and 15 LMS) and hybridized onto Affymetrix Human Gene 1.0 ST arrays. LMS_18b is the same sample as LMS_18a, analyzed at a different time point. LMS_18b data are not included in the final gene expression analysis; and therefore, there is no Sample data table. This sample was instead used in a previous analysis to show that a normalization method (the ComBat algorithm) was successful in removing batch effects and keeping biological variation.

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Undifferentiated pleomorphic sarcoma recapitulates the expressional profile of Subtype II Leiomyosarcoma

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