Genome-wide DNA methylation profiling of primary colorectal laterally spreading tumors identifies disease-specific epi-mutations on common pathways
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PROVIDER: PRJNA417243 | ENA |
REPOSITORIES: ENA
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Project description:Colorectal laterally spreading tumors (LSTs) are rare comparing to adenomas but are becoming more prevalent. Unlike many neoplasms in colons, LST grows to extremely large size, usually greater than 10mm in diameter while rarely invades deeply. Also, there is a low tendency for LSTs to become cancerous. The epigenetic landscape of LST has not been defined. In this study, we used a genome-wide methylation profiling technology, i.e. the Illumina Human Methylation 450K array, to query the main epigenetic difference between LST and para-cancerous samples. Our results suggest that LST displays significant decrease in DNA methylation, especially in some intergenic regions (IGR). By integration of public data for adenomas and colorectal cancers, we defined the commonality and specific epigenetic signatures for these three types of neoplasms in colon, in particular LST and adenomas which represent precancerous conditions. These three diseases shared little specific DNA methylation abnormalities. However, our pathway-level analysis revealed that certain pathways were common targets of epimutation. More interestingly, different diseases seem to employ distinct epigenetic insult to disturb these pathways. Between LST and adenoma, we found eight pathways were commonly targeted but the epi-mutation patterns were opposite between the two diseases. Comparison between precancerous conditions and invasive states revealed the key pathways governing the progression to malignancy, including CAMs and PI3K-Akt pathways.
2019-01-01 | GSE106556 | GEO
Project description:Colorectal laterally spreading tumors (LSTs) grow to extremely large size while rarely invade deeply. Also, there is a low tendency to become cancerous. We used the Illumina Human Methylation 450K array to query the main epigenetic difference of LSTs. We built a discovery cohort with 10 matched cases, and a validation cohort with 9 additional matched cases. Our results suggest that LST displays significant decrease in DNA methylation, highlighted by the discovery of 1,018 hypomethylated intergenic regions (IGRs). Comparing to classic differentially methylated probes and regions that overlap transcription starting site and CpG island, IGR-regions were associated more closely with genes involved in functional biological processes and correlated with specific histone modifications. Hypomethylated IGR regions were often annotated as tissue-specific regulatory elements for noncolon tissues and were typically epigenetically silenced in normal colon mucosa. By integration of public data, we defined the commonality and specific epigenetic signatures for adenomas, LSTs and colon adenocarcinomas. Only 435 hypermethylated differentially methylated probes (DMPs) and differentially methylated regions (DMRs) and 517 hypomethylated DMPs and DMRs were shared by the three diseases. However, our pathway-level analysis discovered that genes in four pathways were common target of epimutations in LSTs, adenomas and CRCs. More interestingly, different diseases seem to employ distinct epigenetic insult to disturb specific pathways. Between LST and adenoma, we found eight pathways including Ras signaling and Rap1 signaling pathway were commonly targeted but the epimutation patterns were opposite. Comparison between precancerous conditions and invasive states revealed the key pathways governing the progression to malignancy, including PI3K-Akt pathways.
| S-EPMC6495531 | biostudies-literature
Project description:This study will evaluate longitudinal performance of Epi proColon with respect to test positivity, longitudinal adherence to Epi proColon screening, adherence to follow-up colonoscopy and diagnostic yield, as well as assay failure rates.
| 2249389 | ecrin-mdr-crc
Project description:We identified and characterized a rice epigenetic mutant Epi-df which exhibits a dwarf stature and various floral defects that are inherited in a dominant fashion. We demonstrated that Epi-df participates in Polycomb repressive complex 2 (PRC2) mediated gene silencing. Epigenetic mutations results in ectopic expression of Epi-df and pleiotropic developmental defects in mutant plants. Moreover, ectopic expression of Epi-df leads to mis-regulated H3K27me3 and changed expression of hundreds of genes involved in a wide range of biological processes. We used microarrays to identify differentially expressed genes in Epi-df. For genome-wide expression analysis of Epi-df, three replicates of WT and Epi-df samples (RNA from 3-week-old seedlings) were analyzed on Affymetrix Genechip® Rice Genome arrays by an Affymetrix service facility (CapitalBio Corporation) according to the manufacturer’s protocols. Genes showing a 2-fold change with a q-value ≤ 0.05 were considered to be differentially expressed.
2012-07-12 | E-GEOD-39298 | biostudies-arrayexpress
Project description:Genetic control of yeast chromatin acetylation epi-polymorphisms
2012-09-21 | E-MTAB-575 | biostudies-arrayexpress
Project description:This experiment has been done to understand the dynamics of gene expression in Sox17.Epi and Endo cells using multiplex RNA-Seq technology. Sox17.Epi (Sox17^GFP+EpCAM+) and Sox17.Endo (Sox17^GFP+EpCAM-) cells were isolated by FACS from E9.5 mouse embryos. The spatial comparison between Sox17.Epi versus Sox17.Endo provides insight into which genes are differentially of specifically expressed in two populations.
2012-07-20 | E-MTAB-970 | biostudies-arrayexpress
Project description:Activating mutations in the Wnt pathway are a characteristic feature of colorectal cancer (CRC). The R-spondin (RSPO) family is a group of secreted proteins that enhance Wnt signaling and RSPO2 and RSPO3 gene fusions have been reported in CRC. We have previously shown that Wnt pathway blockers exhibit potent combinatorial activity with taxanes to inhibit tumor growth. Here we show that RSPO3 antagonism synergizes with paclitaxel based chemotherapies in patient-derived xenograft models (PDX) with RSPO3 fusions and in tumors with common CRC mutations such as APC, β-catenin, or RNF43. In these latter types of tumors that represent over 90% of CRC, RSPO3 is produced by stromal cells in the tumor microenvironment and the activating mutations appear to sensitize the tumors to Wnt-Rspo synergy. The combination of RSPO3 inhibition and taxane treatment provides an approach to effectively target oncogenic WNT signaling in a significant number of patients with colorectal and other intestinal cancers.
| S-EPMC5681666 | biostudies-literature
Project description:Protein tyrosine phosphorylation is an important mechanism that regulates cytoskeleton reorganization and cell spreading of migratory cells. A number of cytoskeletal proteins are known to be tyrosine phosphorylated (pY) in different cellular processes. However, the profile of pY proteins during different stages of cell spreading has not been available.
2016-09-28 | PXD004340 | Pride
Project description:To study the mechanisms of the epithelial-mesenchymal transition (EMT) in prostate cancer metastasis, we first generated an epithelial model cell line derived from prostate cancer epithelial PC3 cells. We isolated a subpopulation of cells that showed a stable epithelial phenotype in culture and designated them PC3-Epi. We next developed mesenchymal cell lines from PC3-Epi cells, through interactions with macrophages. These mesenchymal cell lines were designated PC3-EMT1, PC3-EMT12 and PC3-EMT14. We transfected two of these mesenchymal lines (PC3-EMT1 and PC3-EMT14) with lentiviral ZEB1-shRNA vector (sh4) or the scrambled control (Scr). Consistent with ZEB1's role in EMT and maintenance of the mesenchymal state, silencing of ZEB1 induced the mesenchymal-epithelial transition (MET) in PC3-EMT1 and PC3-EMT14. Cells were plated and allowed to recover for 2 days prior to RNA extraction. PC3-Epi served as a reference sample.
2013-06-14 | E-GEOD-43489 | biostudies-arrayexpress
Project description:DNA methylation and histone H3 lysine 9 dimethylation (H3K9me2) are important epigenetic repression marks for silencing transposons in heterochromatin and regulating gene expression in plant development. However, the mechanistic relationship to other repressive marks, such as histone H3 lysine 27 trimethylation (H3K27me3), is unclear. OsFIE1 (Fertilization Independent Endosperm 1) encodes an Esc-like core component of the Polycomb repressive complex 2 (PRC2), which is involved in H3K27me3-mediated gene repression. Here, we identify a gain-of-function epi-allele (Epi-df) of rice OsFIE1; this allele exhibits a dwarf stature and various floral defects that are inherited in a dominant fashion. We found that Epi-df has no changes in its nucleotide sequence, but is hypo-methylated in the promoter and the 5' region of OsFIE1 and has reduced H3K9me2 and increased H3K4me3. In Epi-df, OsFIE1 was ectopically expressed and its imprinting status was disrupted. OsFIE1 interacted with rice E(z) homologs, consistent with its role in H3K27me3 repression. Ectopic expression of OsFIE1 in Epi-df resulted in alteration of H3K27me3 levels in hundreds of genes. Therefore, this work identifies a novel epi-allele involved in H3K27me3-mediated gene repression, that itself is highly regulated by histone H3K9me2, thereby shedding light on the link between two important epigenetic marks regulating rice development. We report the application of ChIP-Seq technology for high-throughput profiling of histone modifications in WT (wild type) and Epi-df (mutant). We demonstrate that the H3K27me3 status is perturbed at target genes and leads to mis-regulated expression in Epi-df.
2013-12-04 | E-GEOD-40674 | biostudies-arrayexpress