Prognostic DNA Methylation Patterns in CN-AML; a genome wide methylation and gene expression study
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE32252 | GEO | 2011/09/21
SECONDARY ACCESSION(S): PRJNA147349
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE31941: Prognostic DNA Methylation Patterns in Cytogenetically Normal Acute Myeloid Leukemia are predefined by Stem Cell Chromatin Marks [gene expression] GSE32251: Prognostic DNA Methylation Patterns in Cytogenetically Normal Acute Myeloid Leukemia are predefined by Stem Cell Chromatin Marks [methylation] Refer to individual Series
2011-09-20 | E-GEOD-32252 | biostudies-arrayexpress
Project description:Methylated DNA immunoprecipitation followed by high-throughput sequencing (MeDIP-seq) has the potential to identify changes in DNA methylation important in cancer development. In order to understand the role of epigenetic modulation in the development of acute myeloid leukemia (AML) we have applied MeDIP-seq to the DNA of 12 AML patients and 4 normal bone marrows. This analysis revealed leukemia-associated differentially methylated regions that included gene promoters, gene bodies, CpG islands and CpG island shores. Two genes (SPHKAP and DPP6) with significantly methylated promoters were of interest and further analysis of their expression showed them to be repressed in AML. We also demonstrated considerable cytogenetic subtype specificity in the methylomes affecting different genomic features. Significantly distinct patterns of hypomethylation of certain interspersed repeat elements were associated with cytogenetic subtypes. The methylation patterns of members of the SINE family tightly clustered all leukemic patients with an enrichment of Alu repeats with a high CpG density (P < 0.0001). We were able to demonstrate significant inverse correlation between intragenic interspersed repeat sequence methylation and gene expression with SINEs showing the strongest inverse correlation (R2 = 0.7). We conclude that the alterations in DNA methylation that accompany the development of AML affect not only the promoters, but also the non-promoter genomic features, with significant demethylation of certain interspersed repeat DNA elements being associated with AML cytogenetic subtypes. MeDIP-seq data were validated using bisulfite pyrosequencing and the Infinium array.
2012-04-02 | GSE28314 | GEO
Project description:We report the application of methylated DNA immunoprecipitation followed by next-generation sequencing to trisomy 8 AML. Through a global study and quantifying the methylation signals, we demonstrated a characteristic DNA methylation distribution for trisomy 8 indicating the impact of the hypermethylation of the extrachromosome 8 on suppressing the signals on the rest of the chromosomes.
2014-02-13 | GSE38483 | GEO
Project description:Many researchers have reported the prognostic significance of various DNA methylation changes in patients with acute myeloid leukemia (AML). We aimed for a comprehensive evaluation of these epigenetic aberrations that would refine the AML prognostication. We designed a sequencing panel targeting 239 regions described in literature as having a prognostic impact or being commonly associated with AML pathogenesis and analyzed 178 diagnostic samples of AML patients divided into test (n=128) and validation cohort (n=50).
2021-01-26 | GSE165435 | GEO
Project description:BackgroundUveal melanomas are the most common primary intraocular malignant tumors in adults, associated with a high metastasis rate and a low 5-year survival rate. It is a clinic urgency and importance to identify prognostic factors for UVMs.Results55 aberrantly methylated sites of miRNAs and 47 aberrantly methylated sites of lncRNAs were observed between Alive < 2 years group and Alive > 2 years group of UVMs. Two prognostic classifiers were generated. For 13- miRNAs-CpG-classifier, the AUC were 0.958, 0.848 and 0.824 at 1 year, 2 years and 3 years, respectively. For 9- lncRNAs-CpG-classifier, the AUC were 0.943, 0.869 and 0.866 at 1 year, 2 years and 3 years, respectively.ConclusionThe correlation between genome-wide DNA methylation patterns of miRNAs and lncRNAs and the overall survival in UVMs were identified in this study. This novel finding shed new light on developing biomarkers of prognosis for UVMs.MethodsDNA methylation profiles of noncoding miRNAs and lncRNAs for UVMs were accessed from The Cancer Genome Atlas. Then the prognostic value was analyzed by least absolute shrinkage and selection operator method Cox regression and tested by Time-dependent Receiver Operating Characteristic curve.
| S-EPMC6738428 | biostudies-literature
Project description:Rhabdomyosarcoma is the most common soft-tissue sarcoma in children. While cytogenetic abnormalities have been well characterized in this disease, aberrant epigenetic events such as DNA hypermethylation have not been described in genome-wide studies. We have analyzed the methylation status of 25,500 promoters in normal skeletal muscle, and in cell lines and tumor samples of embryonal and alveolar rhabdomyosarcoma from pediatric patients. We identified over 1,900 CpG islands that are hypermethylated in rhabdomyosarcomas relative to skeletal muscle. Genes involved in tissue development, differentiation, and oncogenesis such as DNAJA4, HES5, IRX1, BMP8A, GATA4, GATA6, ALX3, and P4HTM were hypermethylated in both RMS cell lines and primary samples, implicating aberrant DNA methylation in the pathogenesis of rhabdomyosarcoma. Furthermore, cluster analysis revealed embryonal and alveolar subtypes had distinct DNA methylation patterns, with the alveolar subtype being enriched in DNA hypermethylation of polycomb target genes. These results suggest that DNA methylation signatures may aid in the diagnosis and risk stratification of pediatric rhabdomyosarcoma and help identify new targets for therapy.
| S-EPMC3368822 | biostudies-other
Project description:An increasing body of work reveals aberrant hypermethylation of genes occurring in and potentially contributing to the pathogenesis of myeloid malignancies. Several of these diseases, such as myelodysplastic syndromes (MDS), are responsive to DNA methyltransferase inhibitors. In order to determine the extent of promoter hypermethylation in such tumors we compared the distribution of DNA methylation of 14,000 promoters in MDS and secondary AML patients enrolled in a phase I trial of 5-azacytidine and the histone deacetylase inhibitor entinostat against de novo AML patients and normal CD34+ bone marrow cells. The MDS and secondary AML patients displayed more extensive aberrant DNA methylation involving thousands of genes than did the normal CD34+ bone marrow cells or de novo AML blasts. Aberrant methylation in MDS and secondary AML tended to affect particular chromosomal regions, occurred more frequently in Alu poor genes, and included prominent involvement of genes involved in the WNT and MAPK signaling pathways. DNA methylation was also measured at days 15 and 29 after the first treatment cycle. DNA methylation was reversed at day 15 in a uniform manner throughout the genome, and this effect persisted through day 29, even without continuous administration of the study drugs. Keywords: DNA methylation profiling
2009-08-05 | GSE17328 | GEO
Project description:Increasing evidence shows aberrant hypermethylation of genes occurring in and potentially contributing to pathogenesis of myeloid malignancies. Several of these diseases, such as myelodysplastic syndromes (MDSs), are responsive to DNA methyltransferase inhibitors. To determine the extent of promoter hypermethylation in such tumors, we compared the distribution of DNA methylation of 14 000 promoters in MDS and secondary acute myeloid leukemia (AML) patients enrolled in a phase 1 trial of 5-azacytidine and the histone deacetylase inhibitor entinostat against de novo AML patients and normal CD34(+) bone marrow cells. The MDS and secondary AML patients displayed more extensive aberrant DNA methylation involving thousands of genes than did the normal CD34(+) bone marrow cells or de novo AML blasts. Aberrant methylation in MDS and secondary AML tended to affect particular chromosomal regions, occurred more frequently in Alu-poor genes, and included prominent involvement of genes involved in the WNT and MAPK signaling pathways. DNA methylation was also measured at days 15 and 29 after the first treatment cycle. DNA methylation was reversed at day 15 in a uniform manner throughout the genome, and this effect persisted through day 29, even without continuous administration of the study drugs. This trial was registered at www.clinicaltrials.gov as J0443.
| S-EPMC2765680 | biostudies-literature
Project description:Purpose: DNA methylation alterations are early events in tumorigenesis and important in the regulation of gene expression in cancer cells. Lung cancer has in general a poor prognosis, and a deeper insight into the epigenetic landscape in lung adenocarcinoma tumors and its prognostic implications is needed. Experimental Design: We determined whole-genome DNA methylation profiles of 164 lung adenocarcinoma samples and 19 samples of matched normal lung tissue samples using the Illumina Infinium 450K array. The methylation levels were correlated with gene expression levels analyzed by the Agilent 60K mRNA expression array. Methylation changes were studied specifically in tumors from never-smoking patients, and in tumors with mutations in the EGFR-, KRAS- or TP53 genes, and survival analyses were performed. Results: We identified a large number of differentially methylated CpGs in lung adenocarcinoma tissue, and different methylation profiles in tumors from smokers and never-smokers. Specific methylation profiles were observed in tumors with mutations in the EGFR-, KRAS- or TP53 gene. Both positive and negeative correlations between DNA methylation levels and mRNA expression levels were seen. Methylation profiles of the tumor samples identified clusters of patients with distinct prognosis. A prognostic index based on the methylation levels of 33 CpGs was established, and validated in an independent cohort of lung adenocarcinoma patients from the TCGA project. Among the CpGs in the prognostic signature, some were localized in the HOX B and HOX C gene clusters. Conclusions: Methylation differences mirror biological important features the etiology of lung adenocarcinomas and influence prognosis.
2015-11-27 | GSE66836 | GEO
Project description:BACKGROUND: DNA methylation is an epigenetic regulatory mechanism that plays an essential role in mediating biological processes and determining phenotypic plasticity in organisms. Although the horse reference genome and whole transcriptome data are publically available the global DNA methylation data are yet to be known. RESULTS: We report the first genome-wide DNA methylation characteristics data from skeletal muscle, heart, lung, and cerebrum tissues of thoroughbred (TH) and Jeju (JH) horses, an indigenous Korea breed, respectively by methyl-DNA immunoprecipitation sequencing. The analysis of the DNA methylation patterns indicated that the average methylation density was the lowest in the promoter region, while the density in the coding DNA sequence region was the highest. Among repeat elements, a relatively high density of methylation was observed in long interspersed nuclear elements compared to short interspersed nuclear elements or long terminal repeat elements. We also successfully identified differential methylated regions through a comparative analysis of corresponding tissues from TH and JH, indicating that the gene body regions showed a high methylation density. CONCLUSIONS: We provide report the first DNA methylation landscape and differentially methylated genomic regions (DMRs) of thoroughbred and Jeju horses, providing comprehensive DMRs maps of the DNA methylome. These data are invaluable resource to better understanding of epigenetics in the horse providing information for the further biological function analyses.
| S-EPMC4117963 | biostudies-literature