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DNA methylation data from primary neuroblastoma tumors

ABSTRACT: Genome wide DNA methylation profiling of primary neuroblastomas. The Illumina 450k methylation array was used to obtain DNA methylation profiles across approximately 485,000 CpGs in 105 neuroblastomas. Tumors were derived from 40 low-risk, 9 intermediate-risk and 56 high-risk patients. Bisulphite converted DNA from the 105 samples were hybridised to the llumina HumanMethylation450 BeadChip

ORGANISM(S): Homo sapiens

SUBMITTER: Maral Saadati

PROVIDER: E-GEOD-73515 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Integrative Genome-Scale Analysis Identifies Epigenetic Mechanisms of Transcriptional Deregulation in Unfavorable Neuroblastomas.

Henrich Kai-Oliver KO Bender Sebastian S Saadati Maral M Dreidax Daniel D Gartlgruber Moritz M Shao Chunxuan C Herrmann Carl C Wiesenfarth Manuel M Parzonka Martha M Wehrmann Lea L Fischer Matthias M Duffy David J DJ Bell Emma E Torkov Alica A Schmezer Peter P Plass Christoph C Höfer Thomas T Benner Axel A Pfister Stefan M SM Westermann Frank F

Cancer research 20160907 18

The broad clinical spectrum of neuroblastoma ranges from spontaneous regression to rapid progression despite intensive multimodal therapy. This diversity is not fully explained by known genetic aberrations, suggesting the possibility of epigenetic involvement in pathogenesis. In pursuit of this hypothesis, we took an integrative approach to analyze the methylomes, transcriptomes, and copy number variations in 105 cases of neuroblastoma, complemented by primary tumor- and cell line-derived global ...[more]

PMID: 27635046

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Primary neuroblastoma tumors

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

2016-09-08 | E-GEOD-73518 | biostudies-arrayexpress

Interplay between promoter methylation and chromosomal loss in gene silencing at 3p11-p14 in cervical cancer

Project description:We performed integrative methylation, gene dosage and expression profiling to explore the interplay between promoter methylation and loss in gene silencing at 3p11-p14 in cervical cancer. Totally 26 hypermethylated genes were identified by comparing the methylation level of individual CpG sites with corresponding data of normal cervical tissue. Candidate methylation regulated genes in tumors were proposed from the correlation between methylation and gene expression. Integrated analysis of methylation, gene dosage and expression revealed three significant regulation patterns encompassing 8 hypermethylated genes; a methylation driven pattern, a gene dosage driven pattern, and a combined methylation and gene dosage driven pattern. For the LRIG1 gene, patients with both hypermethylation and loss had a worse outcome compared to those harboring only hypermethylation or none of the events. C3orf14 emerged as a novel methylation regulated suppressor gene, for which knockdown was found to promote invasive growth in human papilloma virus (HPV)-transformed keratinocytes. Methylation levels from Illumina 450K methylation arrays were correlated with Illumina gene expression data in cohort 1 and validated in cohort 2.

2015-09-14 | E-GEOD-68339 | biostudies-arrayexpress

Epigenetic profiling in CD4 and CD8 T cells from Gravesâ disease patients reveals changes in genes associated with T cell receptor signaling [methylation]

Project description:In Gravesâ disease (GD), a combination of genetic, epigenetic and environmental factors causes an autoimmune response to the thyroid gland, characterized by lymphocytic infiltrations and autoantibodies targeting the thyroid stimulating hormone receptor (TSHR) and other thyroid antigens. To identify the epigenetic changes involved in GD, we performed a genome-wide analysis of DNA methylation and enrichment of H3K4me3 and H3K27ac histone marks in sorted CD4+ and CD8+ T cells. We found 365 and 3322 differentially methylated CpG sites in CD4+ and CD8+ T cells, respectively. Among the hypermethylated CpG sites, we specifically found enrichment of genes involved in T cell signaling (CD247, LCK, ZAP70, CD3D, CD3E, CD3G, CTLA4 and CD8A) and decreased expression of CD3 gene family members. The hypermethylation was accompanied with the active chromatin histone modifications as we found decreased signals of H3K4me3 and H3K27ac marks at several T cell signaling genes in ChIP-seq analysis. In addition, we found hypermethylation of the TSHR gene first intron, where several GD-associated polymorphisms are located. Our results demonstrate an involvement of dysregulated DNA methylation and histone modifications at T cell signaling genes in GD patients. Individuals were recruited from the Estonian Genome Center of the University of Tartu. Genomic DNA was extracted from sorted CD4+ (31 controls and 36 GD patients) and CD8+ (31 controls and 37 GD patients) T cells. The data collection was performed at the SNP&SEQ Technology Platform in Uppsala University, and data analysis was done at the Institute of Biomedicine and Translational Medicine in the University of Tartu.

2015-11-06 | E-GEOD-71955 | biostudies-arrayexpress

Integrative analysis of methylome and transcriptome in human blood identifies extensive sex and immune cell-specific differentially methylated regions [methylation]

Project description:DNA methylation has an impact on regulation of gene expression, however the relation between the two is complex. By performing an integrative analysis of the methylome and transcriptome of the four main circulating immune cell-subsets from healthy females, namely B cells, monocytes, CD4 and CD8 T cells, the relation between the two was characterized. In addition, in light of the known sex bias in the prevalence of several immune-mediated diseases, the female datasets were compared with similar public available male datasets. Immune subset-specific differentially methylated regions (DMRs) were found to be highly similar between males and females; however numerous sex-specific DMRs shared by the four leukocytes subsets were identified, most located on autosomal chromosomes. This provides a list of highly interesting candidate genes to be studied in diseases with sexual dimorphism like autoimmunity. Immune cell-specific DMRs were mainly located in the gene body and intergenic region, distant from CpG islands but overlapping with enhancer elements, thus indicating the importance of distal regulatory elements in leukocyte subsets. In contrast; sex-specific DMRs were over-represented in CpG islands, suggesting some difference in regulation between sex and immune-cell specificity. Both positive and negative correlations between cell-specific expression and methylation were observed, with negative correlation being more frequent. Our acquired immune cell- and sex- specific methylome and transcriptome profiles provide novel insight on their complex regulatory interactions, and may particularly contribute to research of immune-mediated diseases. DNA purified from isolated 5 cell subsets (monocyte, B cells, CD4 T cells, CD8 T cells and PBMCs) obtained from 6 healthy female donors

2016-07-01 | E-GEOD-71244 | biostudies-arrayexpress

Illumina HumanMethylation450 array data for Ovarian Cancer Samples

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2016-08-11 | E-GEOD-71523 | biostudies-arrayexpress

Genome-wide DNA methylation profiles in progression to in situ and invasive carcinoma of the breast with impact on gene transcription and prognosis

Project description:Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive breast carcinoma (IBC). DNA methylation alterations are thought to be an early event in progression of cancer, and may prove valuable as a tool in clinical decision making and for understanding neoplastic development. Genome-wide DNA methylation profiles of 285 breast tissue samples representing progression of cancer were generated using Illumina HumanMethylation450. Validation of methylation changes between normal and DCIS was performed in an independent dataset of 15 normal and 40 DCIS samples, and validation of a prognostic signature was performed on 583 breast cancer samples from The Cancer Genome Atlas. Using two independent datasets of normal breast tissue and DCIS revealed that DNA methylation profiles of DCIS were radically altered compared to normal breast tissue, involving almost 7000 genes (including CUL7 and ICAM2). Changes between DCIS and IBC involved around 1000 genes. In tumors, DNA methylation was associated with gene expression of almost 3000 genes (p<0.05, Bonferroni corrected) including both negative and positive correlations. A prognostic signature based on methylation level of 18 CpGs (representing genes such as IRF6, TBX5, ZNF259, KCTD21, EPN3, MACF1 and CSNK1G2) was associated to survival of breast cancer patients with invasive tumors, as well as to survival of patients with DCIS and mixed lesions of DCIS and IBC. This work demonstrates that changes in the epigenome occurs early in the neoplastic progression, provide evidence for the possible utilization of DNA methylation based markers of progression in the clinic, and highlights the importance of epigenetic changes in carcinogenesis. Bisulphite converted DNA from the 285 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

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Genome-wide CpG methylation analysis of human white blood cells in obese patients under a weight loss treatment.

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Epigenetic profiling in CD4 and CD8 T cells from Graves disease patients reveals changes in genes associated with T cell receptor signaling

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

2015-11-06 | E-GEOD-71957 | biostudies-arrayexpress

Integrative analysis of methylome and transcriptome in human blood identifies extensive sex and immune cell-specific differentially methylated regions

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

2016-07-01 | E-GEOD-71245 | biostudies-arrayexpress

Genome-wide DNA methylation analysis of seminoma-like TCam-2 cells during transition into an embryonal carcinoma-like state

Project description:Illumina 450k DNA methylation microarray analysis of seminoma-like TCam-2 cells xenografted in nude mice. 2120EP embryonal carcinoma cells served as control. TCam-2 cells acquire pluripotency and become epigenetically reprogrammed to an embryonal carcinoma-like state during in vivo growth. This analysis is part of the article 'BMP inhibition in seminomas initiates acquisition of pluripotency via NODAL signaling resulting in reprogramming to an embryonal carcinoma' by Nettersheim et al., 2015. PLoS Genetics Genomic DNA was isolated from tumors of TCam-2 and 2102EP cells xenografted for 1, 2, 4 and 6 weeks as well as 4 and 8 weeks, respectively. In vivo samples of TCam-2 cells were analyzed in biological duplicates. In vitro cultivated TCam-2 / 2102EP cells as well as 2102EP xenografted for 4 and 8 weeks were analyzed once.

2015-08-01 | E-GEOD-60787 | biostudies-arrayexpress

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