Ontology highlight
ABSTRACT:
PROVIDER: PRJNA353898 | ENA |
REPOSITORIES: ENA
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Project description:Colon polyps represent precursor lesions of colon cancers and their malignant potential varies according to histological subtype. A rare subtype of colon polyps is the Peutz-Jeghers (PJ) polyp. PJ polyps mostly occur in the context of Peutz-Jeghers Syndrome which is characterized by the development of multiple polyps in the intestinal tract and hyperpigmentation of oral mucosa and lips. Peutz-Jeghers Syndrome is an autosomal dominant disorder caused by germline mutations of the Serine Threonin Kinase STK11 (LKB1). PJ polyps very rarely occur outside of Peutz-Jeghers Syndrome and are then referred to as solitary PJ polyps. Contrary to Peutz-Jeghers Syndrome, the genetic basis and the malignant potential of solitary PJ polyps is currently unknown. To date, only one study described a sporadic PJ polyp finding no mutations of STK11, indicating that the molecular profile of solitary PJ polyps differs from Peutz-Jeghers syndrome. Methylome analysis revealed global hypomethylation and CpG island hypermethylation, two features that have been described as hallmarks of the colorectal cancer epigenome. These results provide a paradigm for a premalignant lesion that is defined by epigenetic changes.
2017-01-23 | E-MTAB-5255 | biostudies-arrayexpress
Project description:Genetic and epigenetic alterations are a fundamental aspect of colorectal cancer formation. There is considerable heterogeneity between colorectal cancers regarding the mutations and methylated genes they carry, and this heterogeneity may arise early in the polyp-cancer sequence. However, our understanding of the epigenetic alterations and gene mutations in colon adenomas and their relation to colorectal cancer is incomplete. Thus, we have assessed the methylome in normal colon mucosa, tubular adenomas, and colorectal adenocarcinomas and have determined the relationship of these findings between adenomas and cancer in the colon. Genome-wide alterations in DNA methylation were found in the normal colon mucosa adjacent to colorectal cancer, tubular adenomas, and colorectal cancer. Three subgroups of CRCs and two subgroups of adenomas were identified on the basis of their DNA methylation patterns. The adenomas separated into a high-frequency methylation class (Adenoma-H) and a low-frequency methylation class. The adenoma-H polyps have a methylated DNA signature similar to non-CIMP CRCs, whereas those of the Adenoma-L class have a similar methylation pattern to normal colon mucosa. The CpGs that account for these signatures are located in intragenic/intergenic regions, which suggests that these two groups of adenomas arise from different stem cell populations. We conducted genome-wide array-based studies and comprehensive data analyses of aberrantly methylated loci in 41 normal colon samples, 42 colon adenomas, and 64 colorectal cancers. Supplementary file 'GSE48684_Matrix_signal_intensities_1.txt.gz': includes the unmethylated and methylated signal intensities from Samples GSM1183439-GSM1183561. Supplementary file 'GSE48684_Matrix_signal_intensities_2.txt.gz': includes the unmethylated and methylated signal intensities from Samples GSM1235135-GSM1235158.
2014-09-08 | E-GEOD-48684 | biostudies-arrayexpress
Project description:We evaluated the expression profile of miRNA and snoRNA of normal mucosa in five patients with synchronous CRCs and seven patients with solitary CRCs using the Affymetrix GeneChip miRNA 1.0 array. We found that global dysregulated miRNAs and snoRNAs in normal mucosa between solitary and synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures in normal mucosa between solitary and synchronous CRC, which increases the understanding of the molecular basis of synchronous CRC, and firstly implicates the difference of genetic background in patients with solitary and synchronous CRC.
2015-08-01 | GSE67895 | GEO
Project description:Genetic and epigenetic alterations are a fundamental aspect of colorectal cancer formation. There is considerable heterogeneity between colorectal cancers regarding the mutations and methylated genes they carry, and this heterogeneity may arise early in the polyp-cancer sequence. However, our understanding of the epigenetic alterations and gene mutations in colon adenomas and their relation to colorectal cancer is incomplete. Thus, we have assessed the methylome in normal colon mucosa, tubular adenomas, and colorectal adenocarcinomas and have determined the relationship of these findings between adenomas and cancer in the colon. Genome-wide alterations in DNA methylation were found in the normal colon mucosa adjacent to colorectal cancer, tubular adenomas, and colorectal cancer. Three subgroups of CRCs and two subgroups of adenomas were identified on the basis of their DNA methylation patterns. The adenomas separated into a high-frequency methylation class (Adenoma-H) and a low-frequency methylation class. The adenoma-H polyps have a methylated DNA signature similar to non-CIMP CRCs, whereas those of the Adenoma-L class have a similar methylation pattern to normal colon mucosa. The CpGs that account for these signatures are located in intragenic/intergenic regions, which suggests that these two groups of adenomas arise from different stem cell populations.
2014-09-08 | GSE48684 | GEO
Project description:To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated single-cell chromatin accessibility profiles and single-cell transcriptomes from polyps, normal tissues, and CRCs collected from patients with or without germline APC mutations. We find that a large fraction of polyp and CRC cells exhibit a stem-like phenotype, and we define a continuum of epigenetic and transcriptional changes occurring in these stem-like cells as they progress from homeostasis to CRC.
2022-04-28 | GSE201336 | GEO
Project description:The well-known colorectal adenoma-carcinoma sequence suggests that a normal epithelial cell, through accumulations of genetic lesion and epigenetic disregulation can transform into a benign adenoma then further develop into a cancer. Using microarray-based comparative genomic hybridization (CGH), we reveal genome-wide copy number variations in colorectal cancer and polyp and use them to determine the tissueM-^Rs clonal relationship.
2011-06-30 | E-MEXP-3149 | biostudies-arrayexpress
Project description:A study linking DNA methylation modifications in the normal mucosa of the right colon in individuals with adenomatous polyp formation
| EGAS00001007666 | EGA
Project description:There is much controversy about the role of T-regulatory cells (Treg) in human colon cancer. High densities of tumor-infiltrating Treg can correlate with better or worse clinical outcomes depending on the sutdy. Treg have potent anti-inflammatory functions that have been shown to control cancer progression. However, Treg isolated from patient with colon cancer or in mouse models of polyposis do not have the ability to suppress inflammation and instead promote cancer. Gene expression was preformed to determine differences between Treg isolated from healthy mice and Treg isolated from polyp-ridden mice. Treg (CD4+Foxp3-GFP+) and CD4+ non-Treg (CD4+Foxp3-GFP-) were isolated from various organs of healthy Foxp3-GFP reporter mice or polyp-ridden Foxp3-GFPxAPCΔ468 reporter mice
2012-09-30 | E-GEOD-41229 | biostudies-arrayexpress
Project description:Background an Aim: Epigenetics are thought to play a major role in the carcinogenesis of patients that develop multiple colorectal cancers (CRC) in the non-hereditary setting. Previous studies have suggested concordant DNA hypermethylation between tumor pairs. However, only a few methylation markers have been analyzed. This study was aimed at describing the underlying epigenetic signature that differentiates multiple from solitary colorectal cancer tumors using a genome-scale DNA methylation profiling. Patients and Methods: We used a population-based cohort (EPICOLON II) of 12 patients with synchronous CRC and 29 age- sex- and tumor location-paired solitary CRC patients. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay. The most significantly hypermethylated CpG sites results were validated by Methylight. Tumors samples were also analyzed for the CpG Island Methylator Phenotype (CIMP) using the Infinium DNA methylation data; KRAS and BRAF mutations; microsatellite instability; and immunohistochemistry for MLH1/MSH2/MSH6/PMS2. Functional annotation clustering of differentially methylated genes between multiple and solitary CRCs was performed. Results: We identified 102 CpG sites that showed significant DNA hypermethylation in multiple versus solitary tumors (difference in M-NM-2 value >0.1 and p<0.05). Methylight assays validated the array results for 4 selected significantly hypermethylated genes (MAP1B, HTRA1, ALOX15, TIMP3) identified in the profiling (p=0.0002). Based on the Infinium data, 8/12 (66.6%) of multiple tumors were classified as CIMP-high, as compared to 5/29 (17%) solitary tumors (p=0.004). CIMP-high tumors displayed significant hypermethylation in 301 CpG sites (difference in M-NM-2 value >0.1; p value <0.05). Interestingly, 76/102 (74.5%) of the hypermethylated CpG sites found in multiple vs. solitary tumors were also seen to be hypermethylated in CIMP-H tumors. Functional analysis of hypermethylated genes found in multiple vs. solitary tumors showed the presence and enrichment of genes involved in different tumorigenic functions. Conclusions: Multiple colorectal cancers are associated with a distinct methylation phenotype, with a close association between tumor multiplicity and CIMP-high. Our results may be important to unravel the underlying mechanism of tumor multiplicity in the non-hereditary scenario, and provide novel potential biomarkers for identifying high-risk patients and tailoring surveillance strategies. We used a population-based cohort (EPICOLON II) of 12 patients with synchronous CRC and 29 solitary CRC patients. DNA methylation profiling was performed using the Illumina Infinium HM27 DNA methylation assay.
2014-09-01 | E-GEOD-52573 | biostudies-arrayexpress