Patterns of aberrant DNA methylation after toxicant-induced malignant transformation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE38930 | GEO | 2012/06/26
SECONDARY ACCESSION(S): PRJNA169405
REPOSITORIES: GEO
Similar Datasets
Project description:Aberrant DNA methylation is frequently observed in cancer. The aim of this study was to determine how DNA methylation is changed after arsenic-induced malignant transformation.
2012-06-26 | GSE38929 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE38926: Patterns of aberrant DNA methylation after toxicant-induced malignant transformation (MeDIP-chip dataset 1) GSE38928: Patterns of aberrant DNA methylation after toxicant-induced malignant transformation (MeDIP-chip dataset 2) GSE38929: Patterns of aberrant DNA methylation after toxicant-induced malignant transformation (miRNA dataset) Refer to individual Series
2012-06-25 | E-GEOD-38930 | biostudies-arrayexpress
Project description:Aberrant DNA methylation is frequently observed in cancer. The aim of this study was to determine how DNA methylation is changed after toxicant-induced malignant transformation. This study also puts the DNA methylation changes into context with respect to the aberrant DNA methylation events that occur in bladder and prostate carcinogenesis not associated with toxicant exposure.
2012-06-26 | GSE38928 | GEO
Project description:Aberrant DNA methylation is frequently observed in cancer. The aim of this study was to determine how DNA methylation is changed after toxicant-induced malignant transformation. This study also puts the DNA methylation changes into context with respect to the aberrant DNA methylation events that occur in bladder and prostate carcinogenesis not associated with toxicant exposure.
2012-06-26 | GSE38926 | GEO
Project description:Epigenetic dysfunction is a known contributor in carcinogenesis, and is emerging as a mechanism involved in toxicant-induced malignant transformation for environmental carcinogens such as arsenicals or cadmium. In addition to aberrant DNA methylation of single genes, another manifestation of epigenetic dysfunction in cancer is agglomerative DNA methylation, which can participate in long-range epigenetic silencing that targets many neighboring genes and has been shown to occur in several types of clinical cancers. Using in vitro model systems of toxicant-induced malignant transformation, we found hundreds of aberrant DNA methylation events that emerge during malignant transformation, some of which occur in an agglomerative fashion. In an arsenite-transformed prostate epithelial cell line, the protocadherin (PCDH), HOXC and HOXD gene family clusters are targeted for agglomerative DNA methylation. The agglomerative DNA methylation changes induced by arsenicals appear to be common and clinically relevant events, since they occur in other human cancer cell lines and models of malignant transformation, as well as clinical cancer specimens. Aberrant DNA methylation in general occurred more often within histone H3 lysine-27 trimethylation stem cell domains. We found a striking association between enrichment of histone H3 lysine-9 trimethylation stem cell domains and toxicant-induced agglomerative DNA methylation, suggesting these epigenetic modifications may become aberrantly linked during malignant transformation. In summary, we found an association between toxicant-induced malignant transformation and agglomerative DNA methylation, which lends further support to the hypothesis that epigenetic dysfunction plays an important role in toxicant-induced malignant transformation.
| S-EPMC3499325 | biostudies-literature
Project description:Aberrant DNA methylation is frequently observed in cancer. The aim of this study was to determine how DNA methylation is changed after arsenic-induced malignant transformation. Arsenite-transformed RWPE-1 cells (n=2) are compared to parental RWPE-1 cells (n=2). Normal PrEC (n=2) are included for comparison. Immunoprecipitation using anti-methylcytosine (5MeC) antibody.
2012-06-25 | E-GEOD-38929 | biostudies-arrayexpress
Project description:Aberrant DNA methylation is frequently observed in cancer. The aim of this study was to determine how DNA methylation is changed after toxicant-induced malignant transformation. This study also puts the DNA methylation changes into context with respect to the aberrant DNA methylation events that occur in bladder and prostate carcinogenesis not associated with toxicant exposure. Immortalized UROtsa (n=3) and RWPE-1 (n=2) are compared to normal HUC (n=2) and PrEC (n=2), respectively. Arsenite (n=1), monomethylarsonous acid (n=2) or cadmium (n=1) transformed UROtsa are compared to parental UROtsa (n=3). Arsenite (n=2), cadmium (n=1) or MNU (n=1) transformed RWPE-1 cells are compared to parental RWPE-1 cells (n=2). Clinical bladder tumor biopsies (n=6), urothelial carcinoma cell lines (n=2) and prostate cancer cell lines (n=3) are compared to thier normal tissue counterparts HUC (n=2) and PrEC (n=2). Immunoprecipitation using anti-methylcytosine (5MeC) antibody.
2012-06-25 | E-GEOD-38926 | biostudies-arrayexpress
Project description:Aberrant DNA methylation is frequently observed in cancer. The aim of this study was to determine how DNA methylation is changed after toxicant-induced malignant transformation. This study also puts the DNA methylation changes into context with respect to the aberrant DNA methylation events that occur in bladder and prostate carcinogenesis not associated with toxicant exposure. Immortalized UROtsa (n=3) and RWPE-1 (n=2) are compared to normal HUC (n=2) and PrEC (n=2), respectively. Arsenite (n=1), monomethylarsonous acid (n=2) or cadmium (n=1) transformed UROtsa are compared to parental UROtsa (n=3). Arsenite (n=2), cadmium (n=1) or MNU (n=1) transformed RWPE-1 cells are compared to parental RWPE-1 cells (n=2). Clinical bladder tumor biopsies (n=6), urothelial carcinoma cell lines (n=2) and prostate cancer cell lines (n=3) are compared to thier normal tissue counterparts HUC (n=2) and PrEC (n=2). Immunoprecipitation using anti-methylcytosine (5MeC) antibody.
2012-06-25 | E-GEOD-38928 | biostudies-arrayexpress
Project description:Genome-wide disruption of the epigenetic code is a hallmark of malignancy that encompasses many distinct, highly interactive modifications. Delineating the aberrant epigenome produced during toxicant-mediated malignant transformation will help identify the underlying epigenetic drivers of environmental toxicant-induced carcinogenesis. Gene promoter DNA methylation and gene expression profiling of arsenite-transformed prostate epithelial cells showed a negative correlation between gene expression changes and DNA methylation changes; however, less than 10% of the genes with increased promoter methylation were downregulated. Studies described herein confirm that a majority of the DNA hypermethylation events occur at H3K27me3 marked genes that were already transcriptionally repressed. In contrast to aberrant DNA methylation targeting H3K27me3 pre-marked silent genes, we found that actively expressed C2H2 zinc finger genes (ZNFs) marked with H3K9me3 on their 3' ends, were the favored targets of DNA methylation linked gene silencing. DNA methylation coupled, H3K9me3 mediated gene silencing of ZNF genes was widespread, occurring at individual ZNF genes on multiple chromosomes and across ZNF gene family clusters. At ZNF gene promoters, H3K9me3 and DNA hypermethylation replaced H3K4me3, resulting in a widespread downregulation of ZNF gene expression, which accounted for 8% of all the downregulated genes in the arsenical-transformed cells. In summary, these studies associate toxicant exposure with widespread silencing of ZNF genes by DNA hypermethylation-linked H3K9me3 spreading, further implicating epigenetic dysfunction as a driver of toxicant associated carcinogenesis.
| S-EPMC3891689 | biostudies-literature
Project description:Replicative senescent cells reportedly share similar DNA methylation changes with cancer cells, which are purported to facilitate tumorigenesis in cells bypassing senescence. However, we now report biologically critical and distinct patterns of DNA methylation evolution between replicative and oncogene-induced senescence and transformation in a classic human cell transformation model. While overall DNA methylation losses and gains occur in both replicative senescent and transformed cells, the patterns evolve more programmatically for the former and stochastically for the latter. Oncogene-induced senescence is an acute process involving minimal changes to DNA methylation. The stochastic DNA methylation alterations in transformation mainly involve a set of pro-survival promoter CpG-island methylation events targeting genes controlling development and differentiation processes, while the senescence-specific promoter changes occur in genes involved in positive regulation of cellular biosynthesis and macromolecular metabolism. The above set of pro-survival promoter CpG-island hypermethylation events, but not the senescence-specific events, are prone to occur in primary tumors and aging tissues. Importantly, cells manifest senescence-specific epigenomic patterns very early during commitment to senescence, and while these “near-senescent” cells can be immortalized, they are refractory to transformation by H-Ras oncoprotein (H-rasV12). The senescence-specific methylation is retained during immortalization and transformation attempts, suggesting it does not function to promote tumorigenesis. Thus, abnormalities in cancer-related methylation has their origins in aging and not replicative senescence, and senescence-associated methylation potentially prevents malignant transformation.
2018-01-31 | GSE91069 | GEO