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Cytosine methylation data generated by HELP-tagging from human osteosarcoma biopsy samples

ABSTRACT: Osteosarcoma is the most common primary malignant bone tumor in children. Validated markers for disease prognosis available at diagnosis are lacking. No genome-wide DNA methylation studies linked to clinical outcomes have been reported in osteosarcoma. To address this, we tested the methylome at over 1.1 million loci in 15 osteosarcoma biopsy samples obtained prior to the initiation of therapy and correlated these molecular data with disease outcomes. At the tested loci, samples obtained from patients who experienced disease relapse were generally more methylated than those from patients who did not have recurrence. In samples from patients who went on to have recurrent disease, increased DNA methylation was found at gene bodies, intergenic regions and empirically-annotated candidate enhancers, whereas candidate gene promoters were unusual for a more balanced distribution of increased and decreased DNA methylation. A locus at the TLR4 gene demonstrates one of strongest associations between DNA methylation and five year event-free survival, with empirical annotation of this locus showing promoter characteristics. Our data indicate that DNA methylation information has potential to be predictive of outcome in pediatric osteosarcoma, and that both promoters and non-promoter loci are potentially informative in DNA methylation studies. 15 samples. HpaII libraries were compared to at least 3 MspI libraries from the same sample

ORGANISM(S): Homo sapiens

SUBMITTER: Jeremy Rosenblum

PROVIDER: E-GEOD-59200 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Human cervical cells HELP-tagging cytosine methylation data

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2016-08-22 | E-GEOD-76986 | biostudies-arrayexpress

Liver tissue HELP-tagging cytosine methylation data from C57BL/6J mice receiving high-fat diet with or without lingonberries

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2015-09-20 | E-GEOD-67277 | biostudies-arrayexpress

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2013-07-30 | E-GEOD-42723 | biostudies-arrayexpress

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2014-04-14 | E-GEOD-43705 | biostudies-arrayexpress

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2015-12-22 | E-GEOD-64412 | biostudies-arrayexpress

Human embryonic stem cells HELP-tagging cytosine methylation data (Albert Einstein College of Medicine)

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2010-04-12 | E-GEOD-19937 | biostudies-arrayexpress

Tet1 is a tumor suppressor of hematopoietic malignancy

Project description:Epigenetic pathways that regulate DNA methylation and chromatin modifications are frequently found to be dysregulated in human cancers. The TET methylcytosine dioxygenase 1 (TET1) enzyme is an important regulator of hydroxymethylcytosine (5hmC) in embryonic stem cells, neural progenitors,adult cells and reprogrammed cells. Decreased expression of TET proteins and loss of 5hmC has been reported in many tumors, suggesting a critical role for the maintenance of this epigenetic modification in normal cellular function. However, loss of TET1 function in the etiology of cancer has not been directly investigated. Here, we show that deletion of the Tet1 gene promotes the development of B cell lymphoma. Tet1 is required for maintaining normal levels of 5hmC, preventing aberrant DNA hypermethylation and for the regulation of transcriptional programs involved in B-cell lineage specification, chromosome maintenance, and DNA repair. Progenitor B cells in the absence of Tet1 accumulate DNA damage and whole-exome sequencing of Tet1-deficient tumors revealed a high correlation of mutations with those most frequently found in Non-Hodgkin B cell lymphoma (B-NHL) patients. In addition, we show that the TET1 gene is deleted, hypermethylated and transcriptionally silenced in B-NHL patients. These findings provide the first in vivo evidence of TET1 function as a tumor suppressor of hematopoietic malignancy. We did hydroxymethylation tests for two wild type mice and two Tet1 knockout mice.

2015-04-12 | E-GEOD-65895 | biostudies-arrayexpress

HEK 293T cells HELP-tagging cytosine methylation data treated with 5-aza-2-deoxycytidine

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2015-02-13 | E-GEOD-62592 | biostudies-arrayexpress

A restricted repertoire of cytosine methylation changes in neonates following intrauterine growth restriction

Project description:Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g. type 2 diabetes mellitus; T2DM), manifesting sometimes decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations. Our studies focused specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood, and utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to intrauterine growth restriction (IUGR), but that they are of a substantially lesser degree and involve many fewer loci than the epigenomic dysregulation observed in cancer. This is consistent with a comparable study of individuals born following maternal starvation during the Dutch famine. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4Î± (HNF4A) gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins. Our results give some insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease. Direct comparison of DNA methylation in 10 neonatal CD34+ samples isolated from umbilical cord blood belonging to two groups: IUGR (n=5) and their age-matched controls (n=5). Each microarray consists of a two-color comparison of a methylation-sensitive representation of the genome (HpaII) with an internal methylation-insensitive control/reference (MspI).

2010-02-17 | E-GEOD-17727 | biostudies-arrayexpress

Tissue-specific dysregulation of DNA methylation in aging

Project description:The normal aging process is a complex phenomenon associated with physiological alterations in the function of cells and organs over time. Although an attractive candidate for mediating transcriptional dysregulation, the contribution of epigenetic dysregulation to these progressive changes in cellular function remains unclear. In this study, we employed the genome-wide HELP assay to define patterns of cytosine methylation throughout the rat genome, and the LUMA assay to measure global levels of DNA methylation in the same samples. We studied both liver and visceral adipose tissue, and demonstrated significant differences in DNA methylation with age at >5% of sites analyzed. Furthermore, we showed that epigenetic dysregulation with age is a highly tissue-dependent phenomenon. The most distinctive loci were located at intergenic sequences and conserved non-coding elements, and not at promoters nor at CG-dinucleotide dense loci. Finally, we demonstrated that changes in methylation occur consistently near genes that are involved in metabolism and metabolic regulation, implicating their potential role in the pathogenesis of age-related diseases. We conclude that different patterns of epigenetic dysregulation occur in each tissue over time and may cause some of the physiological changes associated with normal aging. Direct comparison of DNA methylation in 18 samples belonging to four groups: young liver (n=6), young adipose tissue (n=4), old liver (n=5), old adipose tissue (n=3), isolated from F344*BN rats (young at ~3 months, old at ~18 months). Each microarray consists of a two-color comparison of a methylation-sensitive representation of the genome (HpaII) with an internal methylation-insensitive control/reference (MspI).

2010-05-01 | E-GEOD-17332 | biostudies-arrayexpress

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