The spectrum of IDH- and H3-wildtype high-grade glioma subgroups occurring across teenage and young adult patient populations
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ABSTRACT: Methylation array profiling of high grade gliomas occurring in teenagers and young adults between the ages of 13 and 30. This study combines methylation array profiling, whole exam sequencing and fusion panels sequencing to provide and integrated diagnosis of tumours in this age group.
Project description:Methylation array profiling of high grade gliomas occurring in teenagers and young adults between the ages of 13 and 30. This study combines methylation array profiling, whole exome sequencing and fusion panels sequencing to provide and integrated diagnosis of tumours in this age group.
Project description:The MESA Epigenomics and Transcriptomics Study has been launched to investigate potential gene expression regulatory methylation sites in humans by examining the association between CpG methylation and gene expression in purified human monocytes from a large study population (community-dwelling participants in the Multi-Ethnic Study of Atherosclerosis (MESA)). The MESA Epigenomics and Transcriptomics Study was funded by a National Heart, Lung and Blood Institute grant (R01HL101250) through the NIH Roadmap Epigenomics Program in 2009. The current study is particularly focused on the relationships between transcriptomics and methylomics with age. Data includes transcriptomic and methylomic data from CD14+ samples, collected from 1,202 individuals ranging 44 - 83 years of age (Exam 1). Peripheral monocytes were isolated from blood (Exam 5) with anti-CD14 coated magnetic beads, and the Illumina HumanHT-12 v4 Expression BeadChip and the Illumina HumanMethylation450 BeadChip were used to provide genome-wide coverage of mRNA expression and DNA methylation, respectively. This data enabled us to identify CpG loci whose degree of methylation was associated with age (age-DMR),and identify age- and expression-associated methylation sites (age-eMS), whose degree of methylation was associated with age and cis-gene expression (+/- 1Mb), after adjusting for other covariates such as race, gender, study site, and sample contaimination with B-cells, T-cells, natural killer cells, and neutrophils. To estimate residual sample contamination for monocyte data analysis, separate enrichment scores for neutrophils, B cells, T cells, and natural killer cells were calculated and provided as sample characteristics. The participant race, gender, and study site were provided as 'raceGenderSite variable' which represents a combination of those factors. A detailed description of each sample characteristics is included in the 'README.txt'.
Project description:To broaden our understanding of the gene expression common to volar skin, we biopsied the dorsum of the hand, palm, dorsum of the foot and sole and collected DNA for methylation chip anlayses Total of 12 skin biopsy samples with 3 repeats from distinct individuals of each site: dorsum of hand, palm, dorstum of foot and sole. The samples below represent methylation data only.
Project description:Epigenetic remodeling is central to understanding the molecular mechanisms that occur and drive human aging. In fact, DNA methylation clocks are capable of estimating biological age, which determines human lifespan and healthspan. Here, using Illumina's MethylationEPIC array technology, we have profiled the DNA methylation landscape of peripheral whole blood samples from adult individuals ranging in age from 19 to 96 years.
Project description:In this dataset we used the most recent Illumina MethylationEPIC Beadchip platform to describe the genome-wide DNA methylation changes observed upon FOSL2 KO in SEM leukemia cells. In addition, we explored the DNA methylation effect of t(4:11) translocation in the context of CD34+ cells. These samples correspond to additional experimental work from the manuscript and are related to the ArrayExpress entry E-MTAB-8505.
Project description:Genome wide DNA methylation profiling of oligodendroglial tumors (OTs) and five non tumoral brain tissue (NTBT) samples. The Illumina Infinium Human DNA methylation 450k Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in tumoral samples. Samples included 46 OTs and 5 NTBT. Bisulphite converted DNA from the 51 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
Project description:The MESA Epigenomics and Transcriptomics Study has been launched to investigate potential gene expression regulatory methylation sites in humans by examining the association between CpG methylation and gene expression in purified human monocytes and T cells from a large study population (community-dwelling participants in the Multi-Ethnic Study of Atherosclerosis (MESA)). The MESA Epigenomics and Transcriptomics Study was funded by a National Heart, Lung and Blood Institute grant (R01HL101250) through the NIH Roadmap Epigenomics Program in 2009. Data includes transcriptomic and methylomic data from CD4+ samples, collected from 214 individuals. Peripheral T cells were isolated from blood (Exam 5) with anti-CD4 coated magnetic beads, and the Illumina HumanHT-12 v4 Expression BeadChip and the Illumina HumanMethylation450 BeadChip were used to provide genome-wide coverage of mRNA expression and DNA methylation, respectively. This data enabled us to identifyCpG loci whose degree of methylation was associated with age (age-DMR),and identify age- and expression-associated methylation sites (age-eMS), whose degree of methylation was associated with age and cis-gene expression (+/- 1Mb), after adjusting for other covariates such as race, gender, study site, and sample contaimination with B-cells, monocytes, natural killer cells, and neutrophils. To estimate residual sample contamination for monocyte data analysis, separate enrichment scores for neutrophils, B cells, T cells, and natural killer cells were calculated and provided as sample characteristics. The participant race, gender, and study site were provided as 'raceGenderSite variable' which represents a combination of those factors. A detailed description of each sample characteristics is included in the 'README.txt'.
Project description:The Illumina GoldenGate® methylation array was used to evaluate DNA methylation at 1,505 CpG sites in 807 cancer-related genes in 91 consecutive CRC samples and 28 matched normal colonic mucosa. Bisulphite converted DNA from the 119 samples (91 CRC, 28 matched normals) were hybridised to the Illumina GoldenGate® methylation array.
Project description:T-cell lymphoblastic lymphoma (T-LBL) is a heterogeneous malignancy of lymphoblasts committed to T-cell lineage. Dismal outcomes (15-30%) in case of T-LBL relapses warrants for risk-based treatment to be established in future. This is a first comprehensive, systematic, integrated genome-wide analysis including relapse cases aimed towards identifying molecular markers of prognostic relevance for T-LBL. Whole exome sequencing (WES) was performed on “limited cohort” of 16 T-LBL cases which included 6 relapse cases. Validation of WES data was performed on a large cohort (n=131) referred as \\"extended cohort\\". In order to identify copy number alterations and determine the epigenetic changes SNP arrays and methylation arrays were also performed respectively on the \\"limited cohort\\". Activated NOTCH/PI3K-AKT signaling axis and alterations in cell cycle regulators constitutes the core oncogenic program for T-LBL. KMT2D was identified as a prognostic molecular marker, KMT2Dmut and/or PTENmut associated with poor prognosis.
Project description:Methylthioadenosine phosphorylase (MTAP), a key enzyme in the adenine and methionine salvage pathways, catalyzes the hydrolysis of methylthioadenosine (MTA), a compound suggested to affect pivotal cellular processes in part through the regulation of protein methylation. MTAP is expressed in a wide range of cell types and tissues and its deletion is common to cancer cells and in liver injury. The aim of this study was to investigate the proteome and methyl proteome alterations triggered by MTAP deficiency in liver cells to define novel regulatory mechanisms that may explain the pathogenic processes of liver diseases. iTRAQ analysis resulted in the identification of 216 differential proteins (p<0.05) that suggest deregulation of cellular pathways as those mediated by ERK or NFκB. R-methyl proteome analysis lead to the identification of 74 differentially methylated proteins between SK-Hep1 and SK-Hep1+ cells, including 116 new methylation sites. Restoring normal MTA levels in SK-Hep1+ cells parallels the specific methylation of 56 proteins, including KRT8, TGF and CTF8A, which provides a novel regulatory mechanism of their activity with potential implications in carcinogenesis. Inhibition of RNA binding proteins methylation is especially relevant upon accumulation of MTA. As an example, methylation of quaking protein in R242 and R256 in SK-Hep1+ cells may play a pivotal role in the regulation of its activity as indicated by the up-regulation of its target protein p27 kip1. The phenotype associated with a MTAP deficiency was further verified in the liver of MTAP+/- mice. Our data support that MTAP deficiency leads to MTA accumulation and deregulation of central cellular pathways, increasing proliferation and decreasing the susceptibility to chemotherapeutic drugs, which involves differential protein methylation.