Genome-wide DNA methylation profiling of 68 GBM (primary & recurrent), 4 glioma spheres and 5 non-tumor brain samples
ABSTRACT: DNA methylation analysis of 68 glioblastoma specimen of patients treated within clinical trials, 5 samples of normal brain tissue (non-tumor brain) and 4 tumor-derived glioma sphere lines. The data was used to identify changes in DNA methylation which contribute to the aberrant of expression of HOX transcription factors. Our group had previously demonstrated that expression of HOX genes was associated with increased resistance to chemo-radiotherapy and worse outcome in GBM patients Keywords: Disease state comparison Bisulphite converted genomic DNA from the 77 samples were hybridised to the Illumina Infinium 450 Human Methylation Beadchip
Project description:aCGH was used to profile copy-number aberrations (CNA) in 64 glioblastoma specimen of patients treated within clinical trials. The data was used to identify changes in CNA which contribute to the aberrant of expression of HOX transcription factors. Our group had previously demonstrated that expression of HOX genes was associated with increased resistance to chemo-radiotherapy and worse outcome in GBM patients Keywords: Disease state comparison Genomic DNA from the 64 samples and synthetic normal reference DNA were labelled with Cy3 and Cy5 respectively and hybridised to HumArray3 and HumArray2 chips. The unified platform HumArray3.1 is used for annotation purposes
Project description:Our main objective was to study genome-wide differential methylation in de novo glioblastoma multiforme (GBM, grade IV glioma). We evaluated CpG sites in gene promoters of 26,000+ genes using an array-based chip. We retrieved 54 GBM from biorepositories of two institutions(40 from Columbia University and 14 from Case Western Reserve University) and 24 control brain tissues from the New York Brain Bank, which collected control brain tissues from consented subjects without history of neurological diseases at autopsy. Bisulfite modified DNA was extracted from 54 GBM and 24 control brain tissue. The HumanMethylation27 Analysis Bead-Chips (Illumina) were used to interrogate 26,486 informative CpG sites in the autosomes.
Project description:Analysis of gene expression in the bed nucleus of the stria terminalis/preoptic area and striatum in response to perinatal testosterone exposure. The hypothesis tested was that differences in DNA methylation would be reflected in differences in gene expression. Analysis of gene expression in the bed nucleus of the stria terminalis/preoptic area and striatum in response to perinatal testosterone exposure. The hypothesis tested was that differences in DNA methylation would be reflected in differences in gene expression.
Project description:Analysis of DNA methylation in the bed nucleus of the stria terminalis/preoptic area and striatum in response to perinatal testosterone exposure. The hypothesis tested was that treatment of females with testosterone on the day of birth would lead to masculinization of the methylome in adulthood. There were three experimental groups: males, females, and females treated with T on the day of birth. The methylation patterns in each group was determined using reduced representation bisulfite sequencing. Two brain regions and two time points (day 4 and day 60) were surveyed in each group. Each biological replicate is a pool of tissue from three animals.
Project description:Background: Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances in early brain development, and there is mounting evidence to support a role for developmentally-regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development. Results: We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci, particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples. Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that disease-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development. Conclusions: Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects. 33 post-mortem brain (prefrontal cortex) samples (18 schizophrenia cases and 15 controls) were obtained from Douglas Bell-Canada Brain Bank (DBCBB), Montreal, Canada. Bisulfite converted DNA from these samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.0.
Project description:Examine the genetic abnormality in brain tumors Genomic DNA were extracted from frozen brain tumor samples and CGH assay were performed to compare the similarity genomic abnormality among different cell groups.
Project description:We aimed to identify a clinically useful biomarker using DNA methylation-based information to optimize the management of glioblastoma (GBM) patients. We identified a novel six-CpGs signature that predicts the clinical outcome in GBM. The methylation profiling of 79 GBM patients has been used as a validation cohort to demonstrate the performance and the robustness of the identified six-CpGs signature. The status of the “MGMT” biomarker, traditionally used by clinicians to predict survival in GBM, is also indicated per sample.
Project description:This SuperSeries is composed of the following subset Series: GSE24446: Genetic abnormalities in GBM brain tumors GSE24452: Genetic abnormalities in various cell subpopulations of GBM brain tumors GSE24557: Exon-level expression profiles of GBM brain tumors Refer to individual Series