Array CGH analysis of human colorectal tumors
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE35476 | GEO | 2012/08/31
SECONDARY ACCESSION(S): PRJNA156117
REPOSITORIES: GEO
Similar Datasets
Project description:The concept of the CpG island methylator phenotype (CIMP) in colorectal cancers (CRCs) is widely accepted, though the timing of its occurrence and its interaction with other genetic defects early during carcinogenesis remains largely unknown. Our aim was to uncover the molecular evolution of CIMP CRCs through integrative analysis of endoscopic, histological and molecular signatures in precancerous and malignant colorectal lesions. A total of 84 endoscopically obtained human colorectal tumor was analyzed using Agilent CGH microarray. Copy number aberration was compared with clinicopathological features and DNA methylation status.
2012-08-31 | E-GEOD-35476 | biostudies-arrayexpress
Project description:The concept of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) is widely accepted, though the timing of its occurrence and its interaction with other genetic defects are not fully understood. Our aim in this study was to unravel the molecular development of CIMP cancers by dissecting their genetic and epigenetic signatures in precancerous and malignant colorectal lesions.
2012-08-31 | GSE35508 | GEO
Project description:The concept of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) is widely accepted, though the timing of its occurrence and its interaction with other genetic defects are not fully understood. Our aim in this study was to unravel the molecular development of CIMP cancers by dissecting their genetic and epigenetic signatures in precancerous and malignant colorectal lesions. A total of 88 samples (16 normal colon tissues taken from adjacent tumor tissue, 70 colorectal tumor tissues and 2 cell lines) was analyzed using MCA microarray. Aberrant DNA methylation was compared with clinicopathological features and copy number.
2012-08-31 | E-GEOD-35508 | biostudies-arrayexpress
Project description:The CpG island methylator phenotype (CIMP) in colorectal tumors can be recognized by an increased frequency of aberrant methylation in a specific set of genomic loci. Because of the strong association of CIMP with high microsatellite instability (MSI-H), the identification of CIMP+ tumors within microsatellite stable (MSS) colorectal cancers may not be straightforward. To overcome this potential limitation, we have built an improved 7-loci set of methylation markers that includes CACNA1G, IGF2, RUNX3, HTR6, RIZ1, MINT31 and MAP1B. This new set of CIMP markers revealed a bimodal distribution of methylation frequencies in a group of 95 MSS colorectal cancers, which allowed a clearer separation between CIMP classes. Correlation of CIMP+ tumors with bio-pathological traits revealed significant associations with location to the proximal colon, mucinous histology and chromosomal stability. Although not statistically significant, a trend toward an adverse prognosis for CIMP+ cases was observed. Microarray analysis revealed that CIMP+ tumors are characterized by a unique expression profile, a result that confirms that CIMP+ tumors represent a distinct molecular class within MSS colorectal cancers. Moreover, our results suggest that this expression pattern may represent the molecular background for the development of CIMP+ tumors that, in turn, develop MSI when aberrant methylation occurs at the MLH1 gene promoter.
2008-01-01 | E-TABM-328 | 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
Project description:Cancer-specific changes in DNA methylation can alter genetic stability, genomic structure, and gene expression. Promoter CpG island methylation can result in transcriptional silencing and plays an important role in the oncogenic process. We used genome-wide analysis to characterize the methylomes of breast cancers with diverse metastatic behavior. Here, we describe the identification of novel groups of breast tumors characterized by the presence or absence of coordinate hypermethylation at a large number of genes, demonstrating the existence of a breast-CpG island methylator phenotype (B-CIMP). B-CIMP imparts a distinct epigenomic profile and is a strong determinant of metastatic potential. Gene Expression Samples (GSM647057-GSM647077): Twenty-one breast cancer primary samples were analyzed. There are 10 CIMP positive and 11 CIMP negative samples. Methylation Profiling Samples (GSM651372-GSM651410): Thirty-nine breast cancer primary samples were analyzed. There are 17 CIMP positive and 22 CIMP negative samples.
2011-03-31 | E-GEOD-26349 | biostudies-arrayexpress
Project description:Cancer-specific changes in DNA methylation can alter genetic stability, genomic structure, and gene expression. Promoter CpG island methylation can result in transcriptional silencing and plays an important role in the oncogenic process. We used genome-wide analysis to characterize the methylomes of breast cancers with diverse metastatic behavior. Here, we describe the identification of novel groups of breast tumors characterized by the presence or absence of coordinate hypermethylation at a large number of genes, demonstrating the existence of a breast-CpG island methylator phenotype (B-CIMP). B-CIMP imparts a distinct epigenomic profile and is a strong determinant of metastatic potential.
2011-03-31 | GSE26349 | GEO
Project description:Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived xenografts (PDX) are appearing as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. We generated subcutaneous PDX from PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). The extensive multiomics characterization of the xenografts demonstrated that PDX is a suitable model for preclinical studies, representing the diversity of the primary cancers. the variable MultiOmicsClassification indicates the resulting sample's group. Whole-genome DNA methylation was analyzed using the Illumina Infinium HumanMethylation450 Beadchips. Integragen SA (Evry, France) carried out microarray experiments and hybridized to the BeadChip arrays following the manufacturer’s instructions. Illumina GenomeStudio software was used to extract the beta value DNA methylation score for each locus. We removed data from probes that contained SNPs or overlapped with a repetitive element that was not uniquely aligned to the human genome or regions of insertions and deletions in the human genome. The CpG Island Methylator Phenotype (CIMP) index was determined using methylation Illumina Infinium HumanMethylation450 BeadChips based on previous low throughput work (Toyota, 1999). In brief, all island CpG found to be unmethylated (<20% Beta-value) in all 25 normal pancreatic samples from the ICGC consortium (Nones, 2014) were selected. The CIMP index was calculated independently for each sample as the proportion of methylated (>30% Beta-value) CpGs among the selected normally unmethylated island CpG.
2017-12-12 | E-MTAB-5008 | biostudies-arrayexpress
Project description:Promoter hypermethylation divides colon cancers into subtypes with and without a CpG island methylator phenotype (CIMP). Here, we performed genome-wide DNA methylation profiling of colonic normal and tumor tissues to dissect development of CpG hypermethylation in colon carcinogenesis. This identified age-environment related versus genetically driven CpG hypermethylation, the latter being associated with CIMP cancers. We found a strong association between BRAFV600E mutation and downregulation of the DNA demethylases TET1 and TET2. Expression of BRAFV600E in CIMP cancer cells suppressed TET1 transcription, which was sufficient to establish hypermethylation at CIMP genes promoters, including that of TET2. This phenotype was reverted by the BRAFV600E inhibitor vemurafenib. Thus, BRAFV600E, via impairment of cytosine de-methylation, is a genetic driver of CIMP in colon tumorigenesis.
2019-12-18 | GSE124915 | GEO
Project description:Promoter hypermethylation divides colon cancers into subtypes with and without a CpG island methylator phenotype (CIMP). Here, we performed genome-wide DNA methylation profiling of colonic normal and tumor tissues to dissect development of CpG hypermethylation in colon carcinogenesis. This identified age-environment related versus genetically driven CpG hypermethylation, the latter being associated with CIMP cancers. We found a strong association between BRAFV600E mutation and downregulation of the DNA demethylases TET1 and TET2. Expression of BRAFV600E in CIMP cancer cells suppressed TET1 transcription, which was sufficient to establish hypermethylation at CIMP genes promoters, including that of TET2. This phenotype was reverted by the BRAFV600E inhibitor vemurafenib. Thus, BRAFV600E, via impairment of cytosine de-methylation, is a genetic driver of CIMP in colon tumorigenesis.
2019-12-18 | GSE108606 | GEO