DNA hypermethylation in colorectal cancer: Colorectal cancer tissues vs. Adjacent non-tumor tissues
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE33545 | GEO | 2011/11/14
SECONDARY ACCESSION(S): PRJNA148895
REPOSITORIES: GEO
Similar Datasets
Project description:To identify novel hypermethylated genes in colorectal cancer (CRC) and to test their potential application in CRC early diagnosis, we performed a genome-wide screening of 57,723 CpG dinucleotides covering 4,010 genes in paired DNA samples extracted from 3 fresh frozen CRC tissues and their matching non-tumor adjacent tissues from a cohort of 3 CRC patients undergoing curative surgery using MIRA-based microarray. We also validated candidate hypermethylated genes screened by MIRA-based microarray in independent CRC samples using combined bisulfite restriction analysis. A total of 297 CpG dinucleotides in CRC covering 211 genes were found to be hypermethylated in CRC tissues. From these 211 candidate methylated genes, seven novel methylated genes were picked up for validation and three genes were confirmed to be methylated in cancer samples but not in non-cancer samples.We also compared the methylation levels of these three novel hypermethylated genes with those of Vimentin and SEPT9, well-known hypermethylated genes in CRC, and found that methylated PHOX2B, FGF12 and GAD2 were better than methylated Vimentin and SEPT9 in differentiating CRC cancer tissue from normal tissue. Significant enrichment analysis of GO terms of the hypermethylated genes showed that a high proportion of hypermethylated genes in tumor tissues are involved in regulation of transcription. Paired experiments, colorectal cancer tissue vs. adjacent non-cancer tissue. Biological replicates: 3 cancer replicates, 3 paired non-cancer replicates.
2011-11-14 | E-GEOD-33545 | biostudies-arrayexpress
Project description:Determination of the profile of genes commonly aberrantly methylated in colorectal cancer (CRC) has substantial potential value for diagnostic and therapeutic application. However, our knowledge of the DNA methylation pattern in CRC is currently limited. Therefore, we analyzed the methylation profile of 27,578 CpG sites spanning more than 14,000 genes in CRC and in adjacent normal mucosa using beadchip array-based technology. We identified 621 CpG sites located in promoter region and CpG islands that were significantly hypermethylated in CRC compared to normal mucosa. Genes on chromosome 18 showed promoter hypermethylation most frequently. According to gene ontology analysis, the most common biologically relevant class of genes affected by methylation was the class associated with the cadherin signaling pathway. In comparison with genome-wide expression array, mRNA expression was more like to be down-regulated in the genes demonstrating promoter hypermethylation, although this was not statistically significant. We validated 10 CpG sites that were shown to be hypermethylated in the array studies (ADHFE1, BOLL, SLC6A15, ADAMTS5, TFPI2, EYA4, NPY, TWIST1, LAMA1, GAS7) and 2 CpG sites showing hypomethylaion (MAEL, SFT2D3) in CRC compared to normal mucosa using pyrosequencing. The methylation status measured by pyrosequencing was consistent with the methylation array data. In conclusion, we have shown that methylation profiling based on beadchip arrays is an effective method for screening for aberrantly methylated genes in CRC. In addition, we identified novel methylated genes that are candidate diagnostic or prognostic markers for CRC. We measured the methylation status of the 27,578 CpG sites (Human Methylation27 DNA Analysis BeadChip) in 22 pairs of CRC tissue and adjacent normal mucosa to identify genes that are commonly aberrantly methylated in CRC.
2010-06-24 | E-GEOD-17648 | biostudies-arrayexpress
Project description:Determination of the profile of genes commonly aberrantly methylated in colorectal cancer (CRC) has substantial potential value for diagnostic and therapeutic application. However, our knowledge of the DNA methylation pattern in CRC is currently limited. Therefore, we analyzed the methylation profile of 27,578 CpG sites spanning more than 14,000 genes in CRC and in adjacent normal mucosa using beadchip array-based technology. We identified 621 CpG sites located in promoter region and CpG islands that were significantly hypermethylated in CRC compared to normal mucosa. Genes on chromosome 18 showed promoter hypermethylation most frequently. According to gene ontology analysis, the most common biologically relevant class of genes affected by methylation was the class associated with the cadherin signaling pathway. In comparison with genome-wide expression array, mRNA expression was more like to be down-regulated in the genes demonstrating promoter hypermethylation, although this was not statistically significant. We validated 10 CpG sites that were shown to be hypermethylated in the array studies (ADHFE1, BOLL, SLC6A15, ADAMTS5, TFPI2, EYA4, NPY, TWIST1, LAMA1, GAS7) and 2 CpG sites showing hypomethylaion (MAEL, SFT2D3) in CRC compared to normal mucosa using pyrosequencing. The methylation status measured by pyrosequencing was consistent with the methylation array data. In conclusion, we have shown that methylation profiling based on beadchip arrays is an effective method for screening for aberrantly methylated genes in CRC. In addition, we identified novel methylated genes that are candidate diagnostic or prognostic markers for CRC.
2009-08-18 | GSE17648 | GEO
Project description:Methylated genomic fragments from tumor DNA and matching normal control were enriched with the methylated-CpG island recovery assay (MIRA); amplified, labeled and hybridized on Agilent CpG island tiling oligo arrays. MIRA enriched samples from tumor were labeled with Cy5 while MIRA enriched DNA samples from normal tissue were labeled with Cy3. Keywords: Cancer
2009-02-18 | GSE14865 | GEO
Project description:Noninvasive prenatal diagnosis currently used does not achieve desirable levels of sensitivity and specificity. Recently, fetal methylated DNA biomarkers in maternal whole blood have been explored for noninvasive prenatal detection. However, such efforts cover only chromosomal aneuploidy; fetal methylated DNA biomarkers for detecting single-gene disease remain to be discovered. To address this issue, we systematically screened significantly hypermethylated genes in fetal tissues compared with maternal blood for noninvasive prenatal diagnosis of various inherited diseases. First, Methylated-CpG island recovery assay combined with CpG island array was performed in four maternal peripheral bloods and their corresponding placental tissues. Subsequently, direct bisulfite sequencing and combined bisulfite restriction analysis (COBRA) were carried out to validate the reliability of methylation microarray analysis. As results, 310 significantly hypermethylated genes in fetal tissues were detected by microarray. Two of five randomly selected hypermethylated genes detected by microarray were confirmed to be hypermethylated in fetal tissue samples by direct bisulfite sequencing. All four randomly selected hypermethylated genes detected by microarray were confirmed to be hypermethylated in five independent amniotic fluid samples and five independent chorionic villus samples from 10 pregnant women by CORBA. In conclusions, We found a lot of hypermethylated genes and methylation sites in fetal tissues, some of which have great potential to be developed into molecular markers for noninvasive prenatal diagnosis of monogenic disorders. Further clinical study is warranted to confirm these findings. Paired experiments, placental tissues vs. maternal peripheral bloods. Biological replicates: 4 placental tissues and 4 correspoding maternal peripheral bloods.
2012-02-22 | E-GEOD-35997 | biostudies-arrayexpress
Project description:Noninvasive prenatal diagnosis currently used does not achieve desirable levels of sensitivity and specificity. Recently, fetal methylated DNA biomarkers in maternal whole blood have been explored for noninvasive prenatal detection. However, such efforts cover only chromosomal aneuploidy; fetal methylated DNA biomarkers for detecting single-gene disease remain to be discovered. To address this issue, we systematically screened significantly hypermethylated genes in fetal tissues compared with maternal blood for noninvasive prenatal diagnosis of various inherited diseases. First, Methylated-CpG island recovery assay combined with CpG island array was performed in four maternal peripheral bloods and their corresponding placental tissues. Subsequently, direct bisulfite sequencing and combined bisulfite restriction analysis (COBRA) were carried out to validate the reliability of methylation microarray analysis. As results, 310 significantly hypermethylated genes in fetal tissues were detected by microarray. Two of five randomly selected hypermethylated genes detected by microarray were confirmed to be hypermethylated in fetal tissue samples by direct bisulfite sequencing. All four randomly selected hypermethylated genes detected by microarray were confirmed to be hypermethylated in five independent amniotic fluid samples and five independent chorionic villus samples from 10 pregnant women by CORBA. In conclusions, We found a lot of hypermethylated genes and methylation sites in fetal tissues, some of which have great potential to be developed into molecular markers for noninvasive prenatal diagnosis of monogenic disorders. Further clinical study is warranted to confirm these findings.
2012-02-22 | GSE35997 | GEO
Project description:Background: Colorectal cancer (CRC) remains a major concern with high morbidity and mortality worldwide. DNA methylation alteration plays a pivotal role in cancer development. We aimed to screen novel biomarkers for CRC diagnosis and chemotherapy-related adverse event (CRAE) prediction using the advanced Illumina Infinium MethylationEPIC (850K) BeadChip. Methods: We analyzed the methylation profiles of paired tumor and normal tissues from 21 Chinese CRC patients. After normalization by potential confounders, three types of methylation profiles (differentially methylated probes, differentially methylated regions, and gene-function-differentially methylated regions) were further studied by functional annotation and pathway enrichment analysis. At last, integrated-methylation-marker systems for CRC diagnosis and CRAE prediction were developed based on genes within the mostly related pathways and LASSO regression. Findings: Tumor-related methylation was characterized with hypermethylated promoter islands and hypomethylated intragenic openseas. CRAE-related methylation was characterized with hyper- (or hypo-) methylated intragenic (or intergenic) regions. The two most important susceptible factors for various types of CARE were inactive regeneration functions and active immune response. Differentially methylated genes were significantly enriched in neuronal system, metabolism of RNA, and extracellular matrix organization. All of the integrated-methylation-marker systems demonstrated high discriminative accuracy in both CRC diagnosis (AUROC = 1) and CRAE prediction (AUROC = 0.817-1). Interpretation: In this study, we provided new insights on the formation of CRC diagnosis and CRAE based on three types of methylation profile. The integrated-methylation-marker systems combining multiple DMPs were found to have potentially diagnostic and predictive values. Hence, our findings have important clinical implications, and further validation is warranted.
2021-08-01 | GSE159898 | GEO
Project description:Astrocytomas are common and lethal human brain tumors. Here, we have analyzed the methylation status of over 28,000 CpG islands and 18,000 promoters in normal human brain and in astrocytomas of various grades using the methylated-CpG island recovery assay (MIRA). We identified six to seven thousand methylated CpG islands in normal human brain. ~5% of the promoter-associated CpG islands in normal brain are methylated. Promoter CpG island methylation is inversely and intragenic methylation is directly correlated with gene expression levels in brain tissue. In astrocytomas, several hundred CpG islands undergo specific hypermethylation relative to normal brain with 428 methylation peaks common to more than 25% of the tumors. Genes involved in brain development and neuronal differentiation, such as POU4F3, GDNF, OTX2, NEFM, CNTN4, OTP, SIM1, FYN, EN1, CHAT, GSX2, NKX6-1, RAX, PAX6, DLX2, were strongly enriched among genes frequently methylated in tumors. There was an overrepresentation of homeobox genes and 31% of the most commonly methylated genes represent targets of the Polycomb complex. We identified several chromosomal loci in which many (sometimes more than 20) consecutive CpG islands were hypermethylated in tumors. Seven of such loci were near homeobox genes, including the HOXC and HOXD clusters, and the BARHL2, DLX1, and PITX2 genes. Two other clusters of hypermethylated islands were at sequences of recent gene duplication events. Our analysis offers mechanistic insights into brain neoplasia suggesting that methylation of genes involved in neuronal differentiation, perhaps in cooperation with other oncogenic events, may shift the balance from regulated differentiation towards gliomagenesis. Comparison of methylation patterns of 30 astrocytomas and 6 controls
2010-05-16 | E-GEOD-19391 | biostudies-arrayexpress
Project description:Using a methylated-DNA enrichment technique (MIRA) in combination with whole genome tiling arrays, we have characterized by MIRA-chip the entire B cell ‘methylome’ of an individual human at 100 base pair resolution.
2009-01-01 | GSE13700 | GEO
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