Similar Datasets
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
Project description:Overall shared DNA methylation patterns between senescence (Sen) and cancers have led to the model that tumor-promoting epigenetic patterns arise through senescence. We show that transformation-associated methylation changes arise stochastically and independently of programmatic changes during senescence. Promoter hypermethylation events in transformation involve primarily pro-survival and developmental genes, similarly modified in primary tumors. Senescence-associated hypermethylation mainly involves metabolic regulators and appears early in proliferating "near-senescent" cells, which can be immortalized but are refractory to transformation. Importantly, a subset of transformation-associated hypermethylated developmental genes exhibits highest methylation gains at all age-associated cancer risk states across tissue types. These epigenetic changes favoring cell self-renewal and survival, arising during tissue aging, are fundamentally important for stratifying cancer risk and concepts for cancer prevention.
| S-EPMC5813821 | 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 | GSE91070 | GEO
Project description:DNA methylation patterns separate senescence from malignant transformation potential in human cells
| PRJNA356777 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2012-06-26 | GSE38930 | 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:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-07-29 | E-GEOD-55889 | biostudies-arrayexpress
Project description:Meningiomas are central nervous system tumors that originate from the meningeal coverings of the brain and spinal cord. Most meningiomas are pathologically benign or atypical, but 3-5% display malignant features. Despite previous studies on benign and atypical meningiomas, the key molecular pathways involved in malignant transformation remain to be determined, as does the extent of epigenetic alteration in malignant meningiomas. In this study, we explored the landscape of DNA methylation in ten benign, five atypical and four malignant meningiomas. Compared to the benign tumors, the atypical and malignant meningiomas demonstrate increased global DNA hypomethylation. Clustering analysis readily separates malignant from atypical and benign tumors, implicating that DNA methylation patterns may serve as diagnostic biomarkers for malignancy. Genes with hypermethylated CpG islands in malignant meningiomas (such as HOXA6 and HOXA9) tend to coincide with the binding sites of polycomb repressive complexes (PRC) in early developmental stages. Most genes with hypermethylated CpG islands at promoters are suppressed in malignant and benign meningiomas, suggesting the switching of gene silencing machinery from PRC binding to DNA methylation in malignant meningiomas. One exception is the MAL2 gene that is highly expressed in benign group and silenced in malignant group, representing de novo gene silencing induced by DNA methylation. In summary, our results suggest that malignant meningiomas have distinct DNA methylation patterns compared to their benign and atypical counterparts, and that the differentially methylated genes may serve as diagnostic biomarkers or candidate causal genes for malignant transformation.
| S-EPMC3551961 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-06-27 | GSE231780 | 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 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