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Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE52392 | GEO | 2013/11/16

SECONDARY ACCESSION(S): PRJNA227803

REPOSITORIES: GEO

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Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-11-16 | E-GEOD-52392 | biostudies-arrayexpress

Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas.

Project description:BACKGROUND: High-grade soft tissue sarcomas are a heterogeneous, complex group of aggressive malignant tumors showing mesenchymal differentiation. Recently, soft tissue sarcomas have increasingly been classified on the basis of underlying genetic alterations; however, the role of aberrant DNA methylation in these tumors is not well understood and, consequently, the usefulness of methylation-based classification is unclear. RESULTS: We used the Infinium HumanMethylation27 platform to profile DNA methylation in 80 primary, untreated high-grade soft tissue sarcomas, representing eight relevant subtypes, two non-neoplastic fat samples and 14 representative sarcoma cell lines. The primary samples were partitioned into seven stable clusters. A classification algorithm identified 216 CpG sites, mapping to 246 genes, showing different degrees of DNA methylation between these seven groups. The differences between the clusters were best represented by a set of eight CpG sites located in the genes SPEG, NNAT, FBLN2, PYROXD2, ZNF217, COL14A1, DMRT2 and CDKN2A. By integrating DNA methylation and mRNA expression data, we identified 27 genes showing negative and three genes showing positive correlation. Compared with non-neoplastic fat, NNAT showed DNA hypomethylation and inverse gene expression in myxoid liposarcomas, and DNA hypermethylation and inverse gene expression in dedifferentiated and pleomorphic liposarcomas. Recovery of NNAT in a hypermethylated myxoid liposarcoma cell line decreased cell migration and viability. CONCLUSIONS: Our analysis represents the first comprehensive integration of DNA methylation and transcriptional data in primary high-grade soft tissue sarcomas. We propose novel biomarkers and genes relevant for pathogenesis, including NNAT as a potential tumor suppressor in myxoid liposarcomas.

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Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas [methylation]

Project description:We used the Infinium HumanMethylation27 platform to profile DNA methylation in 80 primary, untreated high-grade soft tissue sarcomas, representing eight relevant subtypes, two non-neoplastic fat samples and 14 representative sarcoma cell lines.

2013-11-16 | GSE52391 | GEO

Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas [methylation]

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Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas [gene expression]

Project description:We used the Infinium HumanHT-12 platform to profile gene expression in 79 primary, untreated high-grade soft tissue sarcomas, representing eight relevant subtypes, two non-neoplastic fat samples and 13 representative sarcoma cell lines.

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Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas [gene expression]

2013-11-16 | E-GEOD-52390 | biostudies-arrayexpress

Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas

Project description:Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas

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MicroRNA profiling of primary high-grade soft tissue sarcomas

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Analysis of pulmonary nodules in patients with high-grade soft tissue sarcomas.

Project description:Nowadays, small pulmonary nodules are easily detectable in patients with soft tissue sarcomas (STSs) because of highly improved computed tomography (CT) technologies. The purpose of this study was to determine the frequency and significance of the pulmonary nodules detected by CT in high-grade STS patients. 124 patients with high-grade STS were retrospectively reviewed. There were 72 males (57%) and 52 females (43%). Patients' average age was 61 years (median (quartiles) 66 years (48-75), range 8-94 years). Pulmonary nodules were detected in 49 (39.5%) of 124 patients by CT scanning at first presentation. Of 49 patients with nodules at first presentation, 34 (69.4%) had benign lesions, and 13 (26.5%) had metastatic nodules. One patient (2%) had primary lung cancer and the remaining one with one nodule could not be definitively diagnosed due to a short follow-up time. 30 patients (24.1%) of 124 patients developed pulmonary nodules during their clinical progression. Seven (23.3%) had benign lesions, whereas 21 (70%) had metastatic lesions. Primary lung cancer was detected in two patients (6.7%). The size and timing of detection of a pulmonary nodule significantly affected the final clinical diagnosisby multivariate analysis. We conclude that pulmonary nodules can be detected highly frequently in patients with high-grade STSs because of improved CT technologies. Careful follow-up is needed if nodules are detected after initial treatment or during the clinical course of the disease.

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