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Global methylation analysis of development and progression of colorectal carcinoma

ABSTRACT: Colorectal tumorigenesis proceedes through well defined clinical stages assoicated with charateristic mutations. Besides genetic alterations, epi-driver genes that are aberrantly expressed in cancers in a fashion that confers a seletive growth advantage can also contribute to tumor evolution. To gain a global view of methylation patterns in normal and maliganant colorectal epithelia, we performed genome-wide DNA methylation analysis on DNAs from 48 fresh frozen CRC samples at different stages of CRC progression. We used IlluminaHumanMethylation450 Beadchip to get a broad view of genome-wide DNA methylationdata during CRC progression and identified significantly differentially methylated genes during CRC progression

ORGANISM(S): Homo sapiens

PROVIDER: GSE77954 | GEO | 2016/05/13

SECONDARY ACCESSION(S): PRJNA312196

REPOSITORIES: GEO

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Global methylation analysis of development and progression of colorectal carcinoma

Project description:Colorectal tumorigenesis proceedes through well defined clinical stages assoicated with charateristic mutations. Besides genetic alterations, epi-driver genes that are aberrantly expressed in cancers in a fashion that confers a seletive growth advantage can also contribute to tumor evolution. To gain a global view of methylation patterns in normal and maliganant colorectal epithelia, we performed genome-wide DNA methylation analysis on DNAs from 48 fresh frozen CRC samples at different stages of CRC progression. We used IlluminaHumanMethylation450 Beadchip to get a broad view of genome-wide DNA methylationdata during CRC progression and identified significantly differentially methylated genes during CRC progression A total of 48 macro-dissected tissues including normal colon tissue, adenomas, carcinomas and metastases were collected by the Department of Pathology at the University of Virginia under the supervision of an experienced pathologist. DNA was extracted and run on IlluminaHumanMethylation450 Beadchip by Expression Analyisis.

2016-05-13 | E-GEOD-77954 | biostudies-arrayexpress

Global gene expression analysis of development and progression of colorectal carcinoma

2016-05-13 | GSE77953 | GEO

Global gene expression analysis of development and progression of colorectal carcinoma

Project description:Colorectal cancer (CRC) tumorigenesis proceedes through well defined clinical stages assoicated with charateristic mutations. To get a better understanding of CRC progression at the transcriptional level, we performed transcriptome profiling on samples from normal colonic tissues, pre-malignant adenomas, carcinomas and metatases. We used Affymatrix microarry to get a broad view of gene expression during colorectal cancer progression and identified significantly differentially expressed genes between different stages A total of 58 laser capture micro-dissected tissues that cover the major stages of colorectal cancer progression were collected from the Department of Pathology at the University of Virginia under the supervision of an experienced pathologist. DNA was extracted and run on Affymetrix microarrys. Gene-expression profiles were collected on Affymetrix HG-U133A GeneChips according to the manufacturerâs instructions.

2016-05-13 | E-GEOD-77953 | biostudies-arrayexpress

Methylation-silenced genes in colorectal cancer cell lines

Project description:Using an oligonucleotide array, we undertook a genome-wide search for genes upregulated following treatment with a demethylating agent in two CRC cell lines. Promoter methylation status was determined in 12 CRC cell lines and 11 CRC tissues. After the treatment, 350 genes were upregulated 1.5 fold or more. Six genes (PAGE-5, VCX, MAEL, GAGED2, UCHL1, and GAGE7), which contained putative 5'CpG islands in their promoter regions, were confirmed to be silenced in CRC cell lines. The median level of UCHL1 gene expression in cell lines with methylation was significantly lower than that in cell lines without methylation (P = 0.032). The level of methylation of UCHL1 was significantly higher in tumors than in corresponding normal mucosae (P = 0.005). Chemical genomic screening led to the identification of a specific promoter subject to hypermethylation in CRC. These results suggest that aberrant promoter methylation is the primary mechanism of transcriptional silencing of the UCHL1 gene and that methylation of the UCHL1 gene promoter increases during the development and progression of CRC Keywords: Methylation Analysis This study explored methylation-silenced genes in colorectal cancer (CRC) cell lines. Using an oligonucleotide array, a genome-wide search for genes upregulated following treatment with a demethylating agent, 5-aza-2â??-deoxycitidine, in two CRC cell lines, DLD-1 and HT-29, was performed. Promoter methylation status of candidate genes silenced and upregulated following the treatment was determined in 12 CRC cell linesby methylation-specific PCR.

2010-06-11 | E-GEOD-7687 | biostudies-arrayexpress

Human derived and patient derived xenografts epigenome analysis of primary and metastasis colorectal cancer

Project description:Genome wide DNA methylation profiling of primary (PR) and liver metastasis (LM) colorectal cancer (CRC). The Illumina Infinium MethylationEPIC Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs in human and xenogratfs derived samples. Raw data were processed using R minfi package. The main goal of this study is to develop a methylation-based classifier and predictor for metastatic CRC (mCRC), in order to find specific patients stratification for anti-EGFR targeted therapy (cetuximab) and bring the promise to shed new light on the role of methylation in driving colorectal cancer progression in different groups of patients.

2023-01-31 | GSE208713 | GEO

Genome-wide DNA methylation analysis of colorectal cancer and polyp

Project description:Colorectal polyp is known a precursor of colorectal cancer (CRC) that holds an increased risk for progression to CRC. Circulating cell-free DNA(cfDNA) methylation has shown favorable performance in the detection and monitoring the malignant progression in a variety of cancers. Here, we conducted a study to discovery cfDNA methylation markers for the diagnosis of CRC. We first performed a genome-wide analysis using the Infinium HumanMethylationEPIC BeadChip array to identify differentially methylated CpGs (DMCs) between 8 CRC and 8 polyp tissues. Then, we validated DMCs in a larger tissue cohort and four methylation markers (cg04486886, cg06712559, cg13539460 and cg27541454) were selected as the methylation markers in tissue by LASSO and random forest models. A diagnosis prediction model was bulit based on the four markers and the methylaion diagnosis score (md-score) can effectively discriminate patients with CRC from polyp tissues. Finally, a single cfDNA methylation marker, cg27541454, was confirmed hypermethylated in CRC in the plasma validation cohort. Together, our findings suggested that the md-score derived from tissue could robustly detect CRC from polpy patients, and cg27541454 may be a promising candidate non-invasive biomarker for CRC early diagnosis.

2024-01-01 | GSE220160 | GEO

YTHDF3 improves translation initiation of mRNAs with N6-methyladenosine methylation at 5’ untranslated region by facilitating eIF2AK2 recruitment in oxaliplatin-resistant colorectal cancer

Project description:Oxaliplatin as a first-line drug frequently causes the chemo-resistance on colorectal cancer (CRC). N6-methyladenosine (m6A) methylation has been largely acknowledged in multiple biological functions. However, the molecular mechanisms underlying the m6A methylation in modulating anticancer drug resistance in CRC are still obscure. In present study, RNA-seq was conducted to investigate the transcriptome of CRC tissues from three patients at different disease stages (CapeOx combined chemotherapy sensitivity and resistance).

2022-02-05 | E-MTAB-11323 | biostudies-arrayexpress

Genome-Wide DNA Methylation Profiles of Low- and High-Grade Adenoma Reveals Potential Biomarkers for Early Diagnosis of Colorectal Carcinoma

Project description:Abnormal DNA methylation is a hallmark of human cancers and may be a promising biomarker for early diagnosis of human cancers1. However, the majority of DNA methylation biomarkers that have been identified are based on the hypothesis that early differential methylation regions (DMRs) are maintained throughout carcinogenesis and could be detected at all stages of cancer. In this study, we identified potential early biomarkers of colorectal cancer (CRC) development by genome-wide DNA methylation assay (Illumina infinium450, 450K) to normal (N=20) and pre-colorectal cancer samples including 18 low-grade adenoma (LGA) and 22 high-grade adenoma (HGA).

2020-04-23 | GSE139404 | GEO

Genome-wide total RNA and MBD-sequencing in HCT116 and DKO cells as a global re-expression model [MBD-Seq]

Project description:Genome-wide view of the interplay between methylation and RNA expression in this colorectal cancer model was obtained. MBD-sequencing of 8 colorectal cancer cell lines.

2013-10-01 | E-GEOD-45333 | biostudies-arrayexpress

Epi-genomewide study identifies epigenetic outliers in normal mucosa of colorectal cancer patients

Project description:Genome wide DNA methylation profiling of normal healthy patients and tumor and non-tumor samples of patients with colorectal cancer (CRC). The Illumina Infinium MethylationEPIC BeadChip was used to obtain DNA methylation across ~850,000 CpG sites. Samples include 78 normal sample from CRC patients, 76 tumor samples from CRC patients, and 68 samples from non-CRC patients

2022-03-23 | GSE199057 | GEO

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