Genome-wide profiling of DNA methylation and expression identifies CIMP in myelodysplastic syndrome
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE51759 | GEO | 2013/10/29
SECONDARY ACCESSION(S): PRJNA224960
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-10-29 | E-GEOD-51759 | biostudies-arrayexpress
Project description:To identify genes hypermethylated and transcriptionally downregulated, we have employed the Illumina Infinium HumanMethylation450 BeadChip and Agilent SurePrint G3 Human Gene Expression 8x60K. And we validated selected genes in cases and controls. eventually we estalished CIMP of MDS.
2013-10-29 | GSE51758 | GEO
Project description:To identify genes hypermethylated and transcriptionally downregulated, we have employed the Illumina Infinium HumanMethylation450 BeadChip and Agilent SurePrint G3 Human Gene Expression 8x60K.And we validated selected genes in cases and controls. eventually we estalished CIMP of MDS.
2013-10-29 | GSE51757 | GEO
Project description:To identify genes hypermethylated and transcriptionally downregulated, we have employed the Illumina Infinium HumanMethylation450 BeadChip and Agilent SurePrint G3 Human Gene Expression 8x60K. And we validated selected genes in cases and controls. eventually we estalished CIMP of MDS. Bisulphite converted DNA from the 4 patients and 4 controls were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2013-10-29 | E-GEOD-51758 | biostudies-arrayexpress
Project description:To identify genes hypermethylated and transcriptionally downregulated, we have employed the Illumina Infinium HumanMethylation450 BeadChip and Agilent SurePrint G3 Human Gene Expression 8x60K.And we validated selected genes in cases and controls. eventually we estalished CIMP of MDS. The gene expressions of four cases and four controls were measured.
2013-10-29 | E-GEOD-51757 | biostudies-arrayexpress
Project description:BACKGROUND:Measuring the DNA methylome may offer the opportunity to identify novel disease biomarkers and insights into disease mechanisms. Although aberrant DNA methylation has been investigated in many human cancers and precancerous lesions, the DNA methylation landscape of gastric cardiac intestinal metaplasia (IM) remains unknown. Therefore, we aimed to investigate the genome-wide DNA methylation landscape and to search for potential epigenetic biomarkers of gastric cardiac IM. METHODS:Histopathologic profiling was performed on a total of 118 gastric cardiac biopsies from cancer-free individuals. Genome-wide DNA methylation analysis was performed on 11 gastric cardiac mucosal biopsies (IM?=?7; normal?=?4) using Illumina 850K microarrays. Transcriptional relevance of any candidate epigenetic biomarker was validated by qRT-PCR. RESULTS:The detection rate of gastric cardiac IM was 23% (27/118) in cancer-free individuals. Genome-wide DNA methylation profiling showed a global decrease in methylation in IM compared with normal tissues (median methylation?=?0.64 and 0.70 for gastric cardiac IM and normal tissues, respectively). Differential methylation analysis between gastric cardiac IM and normal tissues identified 38,237 differentially methylated probes (DMPs) with a majority of sites showing hypermethylation in IM compared with normal tissues (56.3% vs. 43.7%). Subsequent analysis revealed a significant enrichment of hypermethylated DMPs in promoter and CpG islands (p?<?0.001 for both, Pearson ?2 test). For DMPs located in promoter CpG islands showing extreme hypermethylation, the candidate gene with the largest number of DMPs (n?=?7) was mapped to HOXA5. Accordingly, mRNA expression of HOXA5 was significantly reduced in IM compared to normal tissue. CONCLUSIONS:Our results suggest the implication of alterations in DNA methylation in gastric cardiac IM and highlight that HOXA5 hypermethylation may be a promising epigenetic biomarker, emphasizing the role of aberrant HOXA5 expression in the pathogenesis of gastric cardiac IM.
| S-EPMC7393819 | biostudies-literature
Project description:The potential mechanism of myelodysplastic syndromes (MDS) progressing to acute myeloid leukemia (AML) remains poorly elucidated. It has been proved that epigenetic alterations play crucial roles in the pathogenesis of cancer progression including MDS. However, fewer studies explored the whole-genome methylation alterations during MDS progression. Reduced representation bisulfite sequencing was conducted in four paired MDS/secondary AML (MDS/sAML) patients and intended to explore the underlying methylation-associated epigenetic drivers in MDS progression. In four paired MDS/sAML patients, cases at sAML stage exhibited significantly increased methylation level as compared with the matched MDS stage. A total of 1090 differentially methylated fragments (DMFs) (441 hypermethylated and 649 hypomethylated) were identified involving in MDS pathogenesis, whereas 103 DMFs (96 hypermethylated and 7 hypomethylated) were involved in MDS progression. Targeted bisulfite sequencing further identified that aberrant GFRA1, IRX1, NPY, and ZNF300 methylation were frequent events in an additional group of de novo MDS and AML patients, of which only ZNF300 methylation was associated with ZNF300 expression. Subsequently, ZNF300 hypermethylation in larger cohorts of de novo MDS and AML patients was confirmed by real-time quantitative methylation-specific PCR. It was illustrated that ZNF300 methylation could act as a potential biomarker for the diagnosis and prognosis in MDS and AML patients. Functional experiments demonstrated the anti-proliferative and pro-apoptotic role of ZNF300 overexpression in MDS-derived AML cell-line SKM-1. Collectively, genome-wide DNA hypermethylation were frequent events during MDS progression. Among these changes, ZNF300 methylation, a regulator of ZNF300 expression, acted as an epigenetic driver in MDS progression. These findings provided a theoretical basis for the usage of demethylation drugs in MDS patients against disease progression.
| S-EPMC7679421 | biostudies-literature
Project description:BackgroundAberrant DNA methylation profiles are a characteristic of all known cancer types, epitomized by the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). Hypermethylation has been observed at CpG islands throughout the genome, but it is unclear which factors determine whether an individual island becomes methylated in cancer.MethodsDNA methylation in CRC was analysed using the Illumina HumanMethylation450K array. Differentially methylated loci were identified using Significance Analysis of Microarrays (SAM) and the Wilcoxon Signed Rank (WSR) test. Unsupervised hierarchical clustering was used to identify methylation subtypes in CRC.ResultsIn this study we characterized the DNA methylation profiles of 94 CRC tissues and their matched normal counterparts. Consistent with previous studies, unsupervized hierarchical clustering of genome-wide methylation data identified three subtypes within the tumour samples, designated CIMP-H, CIMP-L and CIMP-N, that showed high, low and very low methylation levels, respectively. Differential methylation between normal and tumour samples was analysed at the individual CpG level, and at the gene level. The distribution of hypermethylation in CIMP-N tumours showed high inter-tumour variability and appeared to be highly stochastic in nature, whereas CIMP-H tumours exhibited consistent hypermethylation at a subset of genes, in addition to a highly variable background of hypermethylated genes. EYA4, TFPI2 and TLX1 were hypermethylated in more than 90% of all tumours examined. One-hundred thirty-two genes were hypermethylated in 100% of CIMP-H tumours studied and these were highly enriched for functions relating to skeletal system development (Bonferroni adjusted p value =2.88E-15), segment specification (adjusted p value =9.62E-11), embryonic development (adjusted p value =1.52E-04), mesoderm development (adjusted p value =1.14E-20), and ectoderm development (adjusted p value =7.94E-16).ConclusionsOur genome-wide characterization of DNA methylation in colorectal cancer has identified 132 genes hypermethylated in 100% of CIMP-H samples. Three genes, EYA4, TLX1 and TFPI2 are hypermethylated in >90% of all tumour samples, regardless of CIMP subtype.
| S-EPMC5371203 | biostudies-literature
Project description:As a noninvasive blood testing, the detection of cell-free DNA (cfDNA) methylation in plasma has raised an increasing interest due to diagnostic applications. Although extensively used in cfDNA methylation analysis, bisulfite sequencing is less cost-effective. In this study, we investigated the cfDNA methylation patterns in lung cancer patients by MeDIP-seq. Compared with the healthy individuals, 330 differentially methylated regions (DMRs) at gene promoters were identified in lung cancer patients with 33 hypermethylated and 297 hypomethylated regions, respectively. Moreover, these hypermethylated genes were validated with the publicly available DNA methylation data, yielding a set of ten significant differentially methylated genes in lung cancer, including B3GAT2, BCAR1, HLF, HOPX, HOXD11, MIR1203, MYL9, SLC9A3R2, SYT5, and VTRNA1-3. Our study demonstrated MeDIP-seq could be effectively used for cfDNA methylation profiling and identified a set of potential biomarker genes with clinical application for lung cancer.
| S-EPMC6379867 | biostudies-literature
Project description:Irritable bowel syndrome (IBS) is a stress-sensitive disorder. Environmental factors including stress can trigger epigenetic changes, which have not been well-studied in IBS. We performed a pilot study investigating genome-wide DNA methylation of IBS patients and healthy controls (HCs) to identify potential epigenetic markers and associated pathways. Additionally, we investigated relationships of epigenetic changes in selected genes with clinical traits.Twenty-seven IBS patients (59% women; 10 IBS-diarrhea, 8 IBS-constipation, 9 IBS-mixed) and 23 age- and sex-matched HCs were examined. DNA methylation from peripheral blood mononuclear cells (PBMCs) was measured using HM450 BeadChip, and representative methylation differences were confirmed by bisulphite sequencing. Gene expression was measured using quantitative PCR. Gastrointestinal (GI) and non-GI symptoms were measured using validated questionnaires. Associations were tested using non-parametric methods.Genome-wide DNA methylation profiling of IBS patients compared with HCs identified 133 differentially methylated positions (DMPs) (mean difference ?10%; p < 0.05). These genes were associated with gene ontology terms including glutathione metabolism related to oxidative stress and neuropeptide hormone activity. Validation by sequencing confirmed differential methylation of subcommissural organ (SCO)-Spondin (SSPO), glutathione-S-transferases mu 5 (GSTM5), and tubulin polymerization promoting protein genes. Methylation of two promoter CpGs in GSTM5 was associated with epigenetic silencing. Epigenetic changes in SSPO gene were positively correlated with hospital anxiety and depression scores in IBS patients (r > 0.4 and false discovery rate <0.05).This study is the first to comprehensively explore the methylome of IBS patients. We identified DMPs in novel candidate genes which could provide new insights into disease mechanisms; however, these preliminary findings warrant confirmation in larger, independent studies.
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