Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

P16 epimutation modulates the tumor microenvironment and promotes malignancy of Apc-mutant colon cancer

ABSTRACT: We previously generated a mouse model of p16 epimutation (named as p16cis/cis) through targeted knock-in of a 140-bp Alu-related DNA sequence (cis-element) that facilitates the spread of DNA methylation at promoter CpG islands (CGIs) in cis (Yu et al. JCI, 2014). We generated primary mouse embryonic fibroblasts (MEFs) from p16cis/cis and control mice. By whole genome bisulfite sequencing (WGBS) for comprehensive DNA methylation profiling, we showed that cis-element-mediated approach specifically induces p16 promoter hypermethylation.

ORGANISM(S): Mus musculus

PROVIDER: GSE214032 | GEO | 2023/08/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

p16 epimutation modulates the tumor microenvironment and promotes malignancy of Apc-mutant colon cancer (RNA-Seq)

Project description:Using a mouse model of engineered p16 promoter hypermethylation (p16cis/cis), we found that p16 epimutation cooperates with mutant Apc to promote colon cancer development. Therefore, we performed RNA-seq analysis to identify genes regulated by p16 epimutation that contribute to intestinal carcinogenesis.

2023-08-02 | GSE213566 | GEO

p16 epimutation modulates the tumor microenvironment and promotes malignancy of Apc-mutant colon cancer (scRNA-Seq)

Project description:Methylation of p16 promoter resulting in epigenetic gene silencing- known as p16 epimutation- is common in human colorectal cancer (CRC). Using mouse models, we demonstrated that p16 epimutation cooperates with mutant Apc to promote colon cancer development. To comprehensively characterize immune function within the tumor microenvironment (TME), we performed single-cell RNA sequencing (scRNA-seq) of colon tumors in these animals.

2023-08-02 | GSE213567 | GEO

Molecular properties of epimutation hotspots

Project description:Mistakes in the maintenance of CG methylation is a source of heritable epimutations in plants. Multigenerational surveys indicate that the rate of these stochastic events varies substantially across the genome, with some regions harboring localized “epimutation hotspots”. Using Arabidopsis as a model, we show that epimutation hotspots are indexed by a specific set of chromatin states (CS) that map to sub-regions of gene body methylation genes. Although these regions comprise only ~12% of all CGs in the genome, they account for ~63% of all epimutation events per unit time. Molecular profiling revealed that these regions contain unique sequence features, harbor steady-state intermediate methylation levels, and act as putative targets of antagonistic DNA methylation pathways. We further demonstrate that experimentally-induced shifts in steady-state methylation in these hotspot regions are sufficient to significantly alter local epimutation intensities. Our work thus lays foundation for dissecting the molecular mechanisms of epimutation hotspots in plants.

2021-12-02 | GSE178684 | GEO

Genome-wide DNA methylation profiling of colorectal tumours from MLH1 epimutation carriers

Project description:Genome-wide DNA methylation analysis of colorectal tumour samples from 44 FFPE tumour and 15 FFPE normal mucosa samples was performed to invesgitate genome-wide DNA methylation signatures that can distinguish MLH1 epimutation carrier CRCs. This was further applied to resolve clinically challenging CRCs including MLH1 promoter VUS carriers and MLH1 methylated EOCRCs

2023-07-01 | GSE233854 | GEO

Expression data from RCAS PDGFB/Nestin tv-A glioma cells within Ptprd+/+p16-/- (n=2), Ptprd+/-p16-/- (n=2), and Ptrpd-/-p16-/- (n=3) mice.

Project description:PTPRD is a tumor suppressor of glioma that is frequently co-deleted with CDKN2A/p16. We show that Ptprd and p16 cooperate to promote gliomagenesis in the RCAS PDGFB / Nestin tv-A glioma mouse model. We found unique gene expression changes within tumor cells of Ptprd+/-p16-/- vs. Ptprd+/+p16-/- and Ptprd-/-p16-/- tumor cells. Neonatal mice were injected with RCAS PDGFB GFP. At symptoms, or at 12 weeks post injection, GFP+DAPI- tumor cells were sorted for RNA extraction and hybridization on Affymetrix microarrays. The mouse strain used was a mixed background of C57/BL6 and FVB/N. Ptprd mice were from Uetani et al. 2000 and p16/Nestin-tvA mice were from Tchouganouva et al. 2007.

2014-06-02 | E-GEOD-55061 | biostudies-arrayexpress

Divergence among rice cultivars reveals roles for transposition and epimutation in ongoing evolution of genomic imprinting

Project description:To understand the evolution of imprinting mechanisms in the rice species Oryza sativa, we analyzed DNA methylation, transcription and small RNA expression in embryo and endosperm. Cultivars chosen to represent the genetic diversity of cultivated Oryza sativa comprised Nipponbare and Kitaake of the japonica subspecies, and IR64 and 93-11 cultivars of the indica subspecies. While imprinted expression is generally conserved among rice cultivars, approximately 10% of imprinted genes show imprinting divergence across the four cultivars. Analyses of DNA methylation and small RNAs revealed that small RNA producing loci are closely associated with genic regions and four times more likely to be imprinted than genes. However, imprinting divergence most often correlated with DNA methylation epimutations. Correlative epialleles were largely stable within subspecies. Small indels and transposable element insertions were found at half of the epimutated loci and associated with imprinting divergence at half of the remaining loci. Correlating epigenetic and genetic variation occurred at key regulatory regions – the promoter and transcription start site of maternally-biased genes, and the promoter and gene body of paternally-biased genes. Our results reinforce models for the role of maternal-specific DNA hypomethylation in imprint formation at both maternally and paternally biased genes, and highlight the role of transposition events and epimutation in rice imprinting evolution.

2021-06-29 | GSE130122 | GEO

Dominant MLH1 epimutation linked to 5'UTR variant c.-27C>A

Project description:Constitutional epimutations of tumor suppressor genes manifest as promoter methylation and transcriptional silencing of a single allele in normal somatic tissues, thereby predisposing to cancer. Constitutional MLH1 epimutations occur in individuals with young-onset cancer and demonstrate non-Mendelian inheritance through their reversal in the germline. We report a cancer-affected family showing dominant transmission of soma-wide highly mosaic MLH1 methylation and transcriptional repression linked to a particular genetic haplotype. The epimutation was erased in spermatozoa but reinstated in the somatic cells of the next generation. The affected haplotype harbored two single nucleotide substitutions in tandem: c.-27C>A located near the transcription initiation site and c.85G>T. The c.-27C>A variant significantly reduced transcriptional activity in reporter assays and is the probable cause of this epimutation. Five members of a three-generation Caucasian Lynch syndrome family with an autosomal dominant MLH1 epimutation linked to a single nucleotide variant (c.-27C>A) within the MLH1 5'UTR were examined for copy number variations and retention of heterozygosity on chromosome 3. These five carriers of constitutional MLH1 methylation and the c.-27C>A variant were compared with 300 healthy Caucasian controls from the Wellcome Trust Case Control Consortium using three algorithms (QuantiSNP, PennCNV, COKGEN) to detect any copy number variants. The five family members studied were female (the proband II5, her affected mother I1, and three asymptomatic relatives II2, II4 and III2) are labeled according to the pedigree in Figure 3 of the associated publication (Hitchins et al., Cancer Cell, 2011). The supplementary file 'GSE30348_gw6.lrr_baf.txt' contains log R ratio and B-allele frequency values in a tab-delimited format with one marker per row.

2011-07-01 | E-GEOD-30348 | biostudies-arrayexpress

Comparison between HPV+ / p16+ versus the HPV-/p16- from HNSCC patients

Project description:Head and neck squamous cell carcinomas are heterogeneous neoplasms that show clinical and biological differences in association with the human papillomavirus (HPV). To provide adequate therapeutic strategies, biological and clinical characterization is essential to stratify patients based on prognostic and predictive factors. Reports on HNSCC are scarce in Mexico, thus in the present study, we analyze 414 cases of HNSCC, including those of the oropharynx (OPSCC), larynx (LASCC), and oral cavity (OCSCC). We determined the presence of HPV and p16 expression. Global expression profiles were analyzed with Affymetrix HTA 2.0 microarray in 25 selected cases HPV+/p16+ versus HPV-/p16-. In our study we analyze 25 samples derived from HNSCC patients. 18 samples were HPV-/p16- and 7 HPV+/p16+. We compared the HPV-/p16- versus the HPV+/p16+ and identified differentially expressed RNAs with a fold change greater than 1.5 or less than -1.5. These data were used to obtain 98 genes that are differentially expressed in absence of HPV. The present study offers information regarding clinical and molecular characteristics of HNSCC, both associated and unassociated with HPV, in Mexican patients.

2021-12-01 | GSE181805 | GEO

The MLH1 c.-27C>A and c.85G>T variants are borne on a European ancestral haplotype which underlies an autosomal dominant form of MLH1 epimutation.

Project description:Lynch syndrome, caused by germline heterozygous mutations of the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2, or deletions affecting the EPCAM gene upstream of MSH2, is characterized by a predisposition to early-onset colorectal and additional extracolonic cancers. An alternative but rare cause of Lynch syndrome is a constitutional epimutation of MLH1, which is characterized by promoter methylation and transcriptional silencing of a single allele in normal tissues. Worldwide, five families with autosomal dominant transmission of a constitutional MLH1 epimutation linked to an MLH1 haplotype with two single nucleotide variants (c.-27C>A and c.85G>T) have been identified. Array-based genotyping using Affymetrix SNP 6.0 data in four of these families revealed a shared haplotype extending across a ≤2.6 Mb region of chromosome 3p22 encompassing MLH1 and additional flanking genes, indicating common ancestry. Genomic DNA from 5 carriers of the c.-27C>A and c.85G>T variants was hybridized on Affymetrix SNP6.0 array according to manufacturer's procedures

2013-04-01 | E-GEOD-45149 | biostudies-arrayexpress

Expression data from RCAS PDGFB/Nestin tv-A glioma cells within Ptprd+/+p16-/- (n=2), Ptprd+/-p16-/- (n=2), and Ptrpd-/-p16-/- (n=3) mice.

2014-06-02 | GSE55061 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data