DNA copy number changes in fragile regions 3p21 and 16p13.3 in malignant mesothelioma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE57464 | GEO | 2016/11/13
SECONDARY ACCESSION(S): PRJNA246496
REPOSITORIES: GEO
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Project description:Malignant mesothelioma (MM) is an asbestos-related malignancy. Discrimination between MM and reactive mesothelial hyperplasia (RM) is often difficult. MM cells have a broad histological spectrum, and consist mainly of epithelioid, sarcomatoid, and biphasic cell types. The prognosis of MM is generally poor, but better prognosis has been reported with the epithelioid type of MM than the non-epithelioid type. We applied a genome-wide analysis to the identification of new markers that may aid in differentiating the epithelioid type of MM from other histological types and from RM cells.
2014-11-22 | GSE52788 | GEO
Project description:Malignant mesothelioma (MM) is an asbestos-related malignancy. Discrimination between MM and reactive mesothelial hyperplasia (RM) is often difficult. MM cells have a broad histological spectrum, and consist mainly of epithelioid, sarcomatoid, and biphasic cell types. The prognosis of MM is generally poor, but better prognosis has been reported with the epithelioid type of MM than the non-epithelioid type. We applied a genome-wide analysis to the identification of new markers that may aid in differentiating the epithelioid type of MM from other histological types and from RM cells. Array-based comparative genomic hybridization analysis was performed on malignant mesothelioma (MM) primary cell cultures, reactive mesothelial hyperplasia (RM) primary cell cultures; early passage of in vitro primary cell cultures to minimize acquisition of additional genomic changes. If available, matched peripheral blood was applied to analysis.
2014-11-22 | E-GEOD-52788 | biostudies-arrayexpress
Project description:The expression of human microRNAs in the cellular fraction of human peripheral blood of patients with diagnosed malignant mesotheliomas and asbestos-exposed controls. Altered expression of several miRNAs were observed for patients with diagnosed malignant mesotheliomas in comparison with asebstos-expsoed controls. The study group consists of 23 patients with diagnosed malignant mesothelioma (mean age 66 years, range 34 – 84 years). Patients were not treated with chemotherapy or radiation therapy before sample collection. The histological subtypes were: one sarcomatoid, seven biphasic, and twelve epithelioid cases. In three cases the histological subtype was unknown. The control group consists of 17 asbestos-exposed age-matched volunteers without any diagnosed cancer (mean age 68 years, range 47 – 80 years). Oligonucleotide microarrays were purchased from the Norwegican Microarray Consortium (www.microarray.no). The mirVana miRNA Probe Set v2.0 (Ambion) based on the miRBase Sequence Database v8.0. was used.
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Project description:Cross-species investigations of cancer invasiveness are a new approach that has already identified new biomarkers which are potentially useful for improving tumor diagnosis and prognosis in clinical medicine and veterinary science. In this study, we combined proteomic analysis of four experimental rat malignant mesothelioma (MM) tumors with analysis of ten patient-derived cell lines to identify common features associated with mitochondrial proteome rewiring. A comparison of significant abundance changes between invasive and non-invasive rat tumors gave a list of 433 proteins, including 26 proteins reported to be exclusively located in mitochondria. Next, we analyzed the differential expression of genes encoding the mitochondrial proteins of interest in five primary epithelioid and five primary sarcomatoid human MM cell lines; the most impressive increase was observed in the expression of the long-chain acyl coenzyme A dehydrogenase (ACADL). To evaluate the role of this enzyme in migration/invasiveness, two epithelioid and two sarcomatoid human MM cell lines derived from patients with the highest and lowest overall survival were studied. Interestingly, sarcomatoid vs. epithelioid cell lines were characterized by higher migration and fatty oxidation rates, in agreement with ACADL findings. These results suggest that evaluating mitochondrial proteins in MM specimens might identify tumors with higher invasiveness.
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Project description:Malignant mesothelioma (MM) is an asbestos-related malignancy and largely unresponsive to conventional chemotherapy or radiotherapy. Novel, more effective therapeutic strategies are needed for this fatal disease. We performed microarray analysis of MM using Affymetrix Human U133 Plus 2.0 array. Aberrant expression of the genes participating in semaphorin signaling were detected in malignant mesothelioma cells. All MM cells downregulated the expression of more than one gene for SEMA3B, 3F, and 3G when compared with Met5a, a normal pleura-derived cell line. In 12 of 14 epithelioid MM cells, the expression level of SEMA3A was lower than that in Met5a. An augmented expression of VEGFA was detected in half of the MM cells. The expression ratio of VEGFA/SEMA3A was significantly higher in the epithelioid MMs than in Met5a and the non-epithelioid MMs. Next, gene expression profiling for the polycomb and trithorax group genes revealed that expression of BAP1, the catalytic subunit of the polycomb repressive deubiquitinase complex, and many trithorax group genes was downregulated in MMs compared with the expression of the same genes in Met5a cells. Perturbation of the polycomb–trithorax balance plays a significant role in the pathogenesis of malignant mesothelioma.
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Project description:We applied a spatially resolved, high-dimensional transcriptomic approach to study MPM morpho-logical evolution. 139 regions across 8 biphasic MPMs (B-MPMs) were profiled using the GeoMx™Digital Spatial Profiler and Cancer Transcriptome Atlas to compare epithelioid and sarcomatoid components transcriptional profile and reconstruct the positional context of transcriptional activities and the spatial topology of MPM cells interactions.
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Project description:Malignant Mesothelioma (MM) is one of the most lethal human malignancies of the thoracic cavity. We have determined the cell of origin of these tumors by inactivating Nf2 and Trp53 in Cdkn2a-deficient mesothelial cells both in vitro and in vivo. Cloned, in vitro switched cell lines showed distinct protein marker profiles that upon grafting in recipient mice, gave rise to epithelial, sarcomatoid or biphasic MM. We show that corresponding cell types are present in the mesothelial lining, each capable to serve as a cell of origin of one of the distinct MM subtypes of which the RNA expression profile aligns with corresponding human samples. Therefore, the specific target cell is a critical factor in dictating the tumor subtype of MM.
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2015-05-20 | E-GEOD-59066 | biostudies-arrayexpress
Project description:MiRNA screening was performed to identify differentially expressed miRNAs in a series of 14 formalin fixed paraffin-embedded (FFPE) malignant pleural mesothelioma (MPM) samples representative of the epithelioid, biphasic and sarcomatoid histotypes in comparison with normal mesothelium. MiRNA expression in FFPE MPM and normal mesothelial specimens was analyzed through the miRCURY™ LNA™ Array microRNA Profiling Service (Exiqon). RNA samples were subjected to quality control and, subsequently, 450 ng were labelled with the Hy3™ fluorescent label with the miRCURY™ LNA™ Array power labelling kit. A common reference, against which each individual sample could be tested to assay biological variations among the specimens, was constituted by pooling equal amounts of RNA from each tumor and control and labelled with Hy5™. The Hy3™-labelled samples and the Hy5™-labelled reference RNA sample were mixed pair-wise and hybridized to the miRCURY™ LNA™ array version 11.0 (208200-A Exiqon) according to the manufacturer instructions.
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