Project description:We used Illumina Infinium 27k Human DNA Methylation BeadChip v1.2 to assess genome-wide DNA methylation profiling of normal colon epithelial, adenomas and colorectal adenocarcinomas across approximately 27,000 CpGs in fresh frozen colorectal tissue samples. We found that cancer-associated methylation changes with impact on transcription occur nearly as frequent at non-CpG island as CpG island promoters in colorectal cancer (CRC).
Project description:Colorectal carcinoma (CRC) is often characterized by chromosomal instability (CIN) which has been associated with a poor prognosis. Disease-related de novo methylation often causes gene repression that may complement chromosomal losses or mutations. To compare CpG island methylation and chromosomal abnormalities in colorectal cancer, we determineded unbalanced chromosomal changes by aCGH of CRCs that were also profiled for aberrant de novo DNA methylation at 23,000 CpG islands of the human genome (Gebhard et al. 2010; and unpublished data). Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE25221: CpG island methylation in colorectal cancer GSE25228: Chromosomal abnormalities in colorectal cancer
Project description:We used Illumina Infinium 27k Human DNA Methylation BeadChip v1.2 to assess genome-wide DNA methylation profiling of normal colon epithelial, adenomas and colorectal adenocarcinomas across approximately 27,000 CpGs in fresh frozen colorectal tissue samples. We found that cancer-associated methylation changes with impact on transcription occur nearly as frequent at non-CpG island as CpG island promoters in colorectal cancer (CRC). Samples included 6 normal colon epithelial tissue samples, 6 adenomas, and 30 colorectal adenocarcinomas. Bisulfite-converted DNA from the 42 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2.
Project description:A common hallmark of neoplastic cells is abnormal acquisition of CpG island (CGI) methylation and the silencing of associated gene promoters. To determine the extent and distribution of CGI methylation in colorectal cancer, we solexa sequenced MBD affinity purified DNA prepared from five colorectal tumours and matched colon mucosa from the same individuals.
Project description:To identify new markers for colorectal cancer we scrutinized the methylation status by methyl-CpG immunoprecipitation followed by global methylation profiling on a CpG island microarray, as altered expression could drive genomic and chromosomal instability observed in these tumors. We show for the first time hypermethylation of MMP9, DNMT3A, and LIG4 in CRC which was confirmed in two independent ethnic CRC patients groups. Hypermethylation of the LIG4 promoter is a new mechanism to control ligase IV expression. It may represent a new epigenetic marker for colorectal cancer independent of known markers. Methylation profiling in 16 tumors of colorectal cancer patients compared to matched normal tissue of these patients
Project description:To identify new markers for colorectal cancer we scrutinized the methylation status by methyl-CpG immunoprecipitation followed by global methylation profiling on a CpG island microarray, as altered expression could drive genomic and chromosomal instability observed in these tumors. We show for the first time hypermethylation of MMP9, DNMT3A, and LIG4 in CRC which was confirmed in two independent ethnic CRC patients groups. Hypermethylation of the LIG4 promoter is a new mechanism to control ligase IV expression. It may represent a new epigenetic marker for colorectal cancer independent of known markers.
Project description:Colorectal carcinoma (CRC) is often characterized by chromosomal instability (CIN) which has been associated with a poor prognosis. Disease-related de novo methylation often causes gene repression that may complement chromosomal losses or mutations. To compare CpG island methylation and chromosomal abnormalities in colorectal cancer, we determineded unbalanced chromosomal changes by aCGH of CRCs that were also profiled for aberrant de novo DNA methylation at 23,000 CpG islands of the human genome (Gebhard et al. 2010; and unpublished data). This SuperSeries is composed of the SubSeries listed below.
Project description:Genome-wide DNA methylation of colorectal cancer patients with lymph node metastases showed global loss of DNA methylation in CG-poor, non-CpG island (CGI) regions. Overall CGI methylation was increased in tumour samples. Differential methylation analysis of CGIs identified 60 putative biomarkers, with >20% increase in DNA methylation in both primary tumour and metastasis samples compared to normal adjacent tissue.
Project description:Background: Researching the murine epigenome in disease models has been hampered by the lack of an appropriate and cost-effective DNA methylation array. Until recently, investigators have been limited to the relatively expensive and analysis intensive bisulphite sequencing methods. Here, we performed a comprehensive, comparative analysis between the new Mouse Methylation BeadChip (MMB) and reduced representation bisulphite sequencing (RRBS) in two murine models of colorectal carcinogenesis, providing insight into the utility to each platforms in a real world environment. Results: We captured 1.47x106 CpGs by RRBS and 2.64x105 CpGs by MMB, mapping to 13,778 and 13,365 CpG islands, respectively. RRBS captured significantly more CpGs per island (median 41 for RRBS versus 2 for MMB). We found that 64.4% of intra-island CpG methylation variability can be captured by measuring approximately one quarter of CpG island (CGI) CpGs. MMB was more precise in measuring DNA methylation, especially at sites that had low RRBS coverage. This impacted differential methylation analysis, with more statistically significantly differentially methylated CpG sites identified by MMB in all experimental conditions, however the difference was minute when appropriate thresholding for the magnitude of methylation change (0.2 beta value difference) was applied, providing confidence that both techniques can identify similar differential DNA methylation. Gene ontology enrichment analysis of differentially hypermethylated gene promoters identified similar biological processes and pathways by both RRBS and MMB across two murine model systems. Conclusion: MMB is an effective tool for profiling the murine methylome that performs comparably to RRBS, identifying similar differentially methylated pathways. Although MMB captures a similar proportion of CpG islands, it does so with fewer CpGs per island. We show that subsampling informative CpGs from CpG islands is an appropriate strategy to capture whole island variation. Choice of technology is experiment dependent and will be predicated on the underlying biology being probed.