Methylation analysis of 81 glioma clinical samples (49 CIMP+ and 32 CIMP-) and 53 cell line samples
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE30338 | GEO | 2012/02/16
SECONDARY ACCESSION(S): PRJNA154817
REPOSITORIES: GEO
Similar Datasets
Project description:Glioma CIMP (G-CIMP) is a powerful determinant of tumor pathogenicity but the molecular cause of G-CIMP is a fundamental question that is unresolved. Here, we show that mutation of a single gene, isocitrate dehydrogenase 1 (IDH1), directly causes the G-CIMP in gliomas by remodeling the methylome. In this study 81 glioma clinic samples (49 CIMP+ and 32 CIMP-) were analyzed. Parental IDH1 wild-type and IDH1 mutant cells were passaged until passage 50.
2012-02-16 | E-GEOD-30338 | biostudies-arrayexpress
Project description:Glioma CIMP (G-CIMP) is a powerful determinant of tumor pathogenicity but the molecular cause of G-CIMP is a fundamental question that is unresolved. Here, we show that mutation of a single gene, isocitrate dehydrogenase 1 (IDH1), directly causes the G-CIMP in gliomas by remodeling the methylome. In this study 52 glioma clinic samples (36 CIMP+ and 16 CIMP-) were analyzed. Parental IDH1 wild-type and IDH1 mutant cells were passaged 40 and passage 40 were cell line was sent for expression array.
2012-02-16 | E-GEOD-30336 | biostudies-arrayexpress
Project description:Glioma CIMP (G-CIMP) is a powerful determinant of tumor pathogenicity but the molecular cause of G-CIMP is a fundamental question that is unresolved. Here, we show that mutation of a single gene, isocitrate dehydrogenase 1 (IDH1), directly causes the G-CIMP in gliomas by remodeling the methylome.
2012-02-16 | GSE30336 | GEO
Project description:The cytosolic NADP+-dependent isocitrate dehydrogenase IDH1 is frequently mutated in human cancers. Recent studies have shown that IDH1 mutant primary glioblastomas (GBM) and acute myeloid leukemias (AML) display robust association with CpG island methylator phenotype (CIMP). Such observations bring into question whether IDH1 mutations directly contribute to the development of CIMP or if the hypermethylation phenotype precedes acquisition of IDH1 mutations. To reveal the effects of IDH1 mutations on DNA methylation and gene expression, we introduced the most frequently observed IDH1 mutation, R132H, into a human cancer cell line through gene targeting. We profiled changes in methylation at over 27,000 CpG dinucleotides spanning 14,475 unique gene regions and characterized genome-wide gene expression alterations resulting from IDH1R132H knockin. We observed consistent changes in both DNA methylation and gene expression when comparing two independent IDH1R132H knockin clones to their wild-type parent, and report hypermethylation of over 2,000 loci, the majority of which contained preexisting methylation in IDH1WT parental cells. These loci exhibit the same trend in primary TCGA glioblastoma tumors with mutant IDH1 as compared to those with wild-type IDH1 and have significant overlap with genes hypermethylated in glioma-CIMP+ tumors. Furthermore, we identify specific DNA methylation and gene expression alterations which correlate with IDH1 mutations in our cell-line model as well as primary glioblastomas, including hypermethylation and transcriptional silencing of RBP1. The presented data provide insight on epigenetic alterations induced by IDH1 mutations and support a contributory role for IDH1 mutants in regulation of DNA methylation and gene expression in human cancer cells. Comparison of IDH1 R132H and wild-type HCT116 cells as well as HOG cells overexpressing either wild-type IDH1 or IDH1 R132H
2012-08-13 | E-GEOD-31133 | biostudies-arrayexpress
Project description:The cytosolic NADP+-dependent isocitrate dehydrogenase IDH1 is frequently mutated in human cancers. Recent studies have shown that IDH1 mutant primary glioblastomas (GBM) and acute myeloid leukemias (AML) display robust association with CpG island methylator phenotype (CIMP). Such observations bring into question whether IDH1 mutations directly contribute to the development of CIMP or if the hypermethylation phenotype precedes acquisition of IDH1 mutations. To reveal the effects of IDH1 mutations on DNA methylation and gene expression, we introduced the most frequently observed IDH1 mutation, R132H, into a human cancer cell line through gene targeting. We profiled changes in methylation at over 27,000 CpG dinucleotides spanning 14,475 unique gene regions and characterized genome-wide gene expression alterations resulting from IDH1R132H knockin. We observed consistent changes in both DNA methylation and gene expression when comparing two independent IDH1R132H knockin clones to their wild-type parent, and report hypermethylation of over 2,000 loci, the majority of which contained preexisting methylation in IDH1WT parental cells. These loci exhibit the same trend in primary TCGA glioblastoma tumors with mutant IDH1 as compared to those with wild-type IDH1 and have significant overlap with genes hypermethylated in glioma-CIMP+ tumors. Furthermore, we identify specific DNA methylation and gene expression alterations which correlate with IDH1 mutations in our cell-line model as well as primary glioblastomas, including hypermethylation and transcriptional silencing of RBP1. The presented data provide insight on epigenetic alterations induced by IDH1 mutations and support a contributory role for IDH1 mutants in regulation of DNA methylation and gene expression in human cancer cells. Comparison of IDH1 R132H and wild-type HCT116 cells
2012-08-13 | E-GEOD-31126 | biostudies-arrayexpress
Project description:A method (termed Cellular Imprinting Proteomics, CImP) for the identification and quantification of the ocular surface proteome using a minimally invasive membrane filter device is described. Moreover, The CImP method was applied to profile the molecular alterations in the eyes of infants exposed to Zika virus (ZIKV) infection during gestation.
2020-07-23 | PXD014038 | Pride
Project description:The CpG island methylator phenotype (CIMP) in colorectal tumors can be recognized by an increased frequency of aberrant methylation in a specific set of genomic loci. Because of the strong association of CIMP with high microsatellite instability (MSI-H), the identification of CIMP+ tumors within microsatellite stable (MSS) colorectal cancers may not be straightforward. To overcome this potential limitation, we have built an improved 7-loci set of methylation markers that includes CACNA1G, IGF2, RUNX3, HTR6, RIZ1, MINT31 and MAP1B. This new set of CIMP markers revealed a bimodal distribution of methylation frequencies in a group of 95 MSS colorectal cancers, which allowed a clearer separation between CIMP classes. Correlation of CIMP+ tumors with bio-pathological traits revealed significant associations with location to the proximal colon, mucinous histology and chromosomal stability. Although not statistically significant, a trend toward an adverse prognosis for CIMP+ cases was observed. Microarray analysis revealed that CIMP+ tumors are characterized by a unique expression profile, a result that confirms that CIMP+ tumors represent a distinct molecular class within MSS colorectal cancers. Moreover, our results suggest that this expression pattern may represent the molecular background for the development of CIMP+ tumors that, in turn, develop MSI when aberrant methylation occurs at the MLH1 gene promoter.
2008-01-01 | E-TABM-328 | biostudies-arrayexpress
Project description:Glioblastomas (GBMs) are divided into CpG Island Methylator Phenotype (CIMP) and non-CIMP tumors. Non-CIMP GBMs derive from cells with non-disjunction of chromosome (chr7) and chromosome 10 (chr10), resulting in chr7 gain and chr10 loss, while CIMP GBMs have mutations in isocitrate dehydrogenase 1 or 2 (IDH1/2). Gain of chr7 is largely driven by PDGFA, but other genes on chr7 are likely to contribute to fitness gains and aggressiveness of these GBMs. We computationally investigated genes on chr7 whose gene expression correlated with survival, identifying HOXA5 as a potential driver of proneural gliomagenesis. Using a combination of human GBM cells and mouse PDGF-driven gliomas, we showed that HOXA5 drives increased proliferation and radiation resistance in culture and in vivo. These phenotypes appear to be in part due to effects on p53 and other apoptosis-related genes.
2018-04-09 | GSE89409 | GEO
Project description:Gliomas harboring mutations in isocitrate dehydrogenase 1/2 (IDH1/2) have the CpG island methylator phenotype (CIMP) and significantly longer patient survival time than wild-type IDH1/2 tumors. Although there are many factors underlying the differences in survival between these two tumor types, immune-related differences in cell content are potentially important contributors. In order to investigate the role of IDH mutations in immune response, we created a syngeneic pair mouse model for mutated IDH1 (mutIDH1) and wild-type IDH1 (wtIDH1) gliomas and demonstrated that muIDH1 mice showed many molecular and clinical similarities to muIDH1 human gliomas, including a 100-fold higher concentration of 2-hydroxygluratate (2-HG), longer survival time, and higher CpG methylation compared to wtIDH1. Also, we showed that IDH1 mutations caused downregulation of leukocyte chemotaxis, resulting in repression of the tumor-associated immune system. Given that significant infiltration of immune cells such as macrophages, microglia, monocytes, and neutrophils is linked to poor prognosis in many cancer types, these reduced immune infiltrates in muIDH1 glioma tumors may contribute in part to the differences in aggressiveness of the two glioma types.
2017-05-21 | GSE96979 | GEO
Project description:The recent discovery of mutations in metabolic enzymes has rekindled interest in harnessing the altered metabolism of cancer cells for cancer therapy. One potential drug target is isocitrate dehydrogenase 1 (IDH1) which is mutated in multiple human cancers. Here, we examine the role of mutant IDH1 in fully transformed cells with endogenous IDH1 mutations. A selective R132H-IDH1 inhibitor (AGI-5198) identified through a high-throughput screen dose-dependently blocked the ability of the mutant enzyme (mIDH1) to produce R-2-hydroxyglutarate (R-2HG). Under conditions of near complete R-2HG inhibition, the mIDH1 inhibitor induced demethylation of histone H3K9M3 and expression of genes associated with gliogenic differentiation. Blockade of mIDH1 impaired the growth of IDH1-mutant - but not IDH1-wildtype – glioma cells without appreciable changes in genome wide DNA methylation. These data suggest that mIDH1 may promote glioma growth through mechanisms beyond its well-characterized epigenetic effects.
2013-04-04 | GSE45198 | GEO