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Neighboring genomic regions influence differential methylation patterns of CpG islands in endometrial and breast cancers

ABSTRACT: We report the global methylation patterns by MBDCap-seq for total 232 primary samples in endometrial cohorts, breast cancer cohorts and breast cancer cell lines. We found total 1,007 differentially methylated regions (DMRs) include CpG islands and shores in endometrial cohorts, and 2529 for Breast Cancer cohorts. We also identified 153 regions that are distinctly different from regular CpG islands at the 5'-ends of genes. Those regions, always contain a chain of 1-2 main islands and a few satellites alone on GC-poor and gene-less region. Majority of CpG atolls contain lowly transcribed or silenced genes in normal controls. This phenomenon provides a new opportunity to develop sensitive biomarkers for cancer diagnosis and prognosis

ORGANISM(S): Homo sapiens

PROVIDER: GSE26592 | GEO | 2012/01/11

SECONDARY ACCESSION(S): PRJNA136187

REPOSITORIES: GEO

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Homo sapiens

Project description:Neighboring genomic regions influence differential methylation patterns of CpG islands in endometrial and breast cancers

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Methylation detection Oligonucleotide Microarray Analysis: high resolution method for CpG island methylation detection 1

Project description:Methylation of CpG islands associated with genes can affect the expression of the proximal gene, and methylation of non associated CpG islands correlates to genomic instability. This epigenetic modification has been shown to be important in many pathologies, from development and disease to cancer. We report the development of a novel high-resolution microarray that detects the methylation status of over 25,000 CpG islands in the human genome. Experiments were performed to demonstrate low system noise in the methodology and that the array probes have a high signal to noise ratio. Methylation measurements between different cell lines were validated demonstrating the accuracy of measurement. We then identified alterations in CpG islands, both those associated with gene promoters, as well as non-promoter associated islands in a set of breast and ovarian tumors. We demonstrate that this methodology accurately identifies methylation profiles in cancer and in principle it can differentiate any CpG methylation alterations and can be adapted to analyze other species. We have developed a method to profile genome wide methylation. 12 breast normal samples and matching tumors from these individuals and an additional 28 tumor samples from other individuals were analyzed for CpG methylation. After inter array normalization, the tumor samples were taken together and the methylation compared to that of the normal samples to identify regions of the CpG islands that are significantly altered between the two datasets. Some of these regions were validated for their methylation as a proof of principle for the method.

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Methylation detection Oligonucleotide Microarray Analysis: high resolution method for CpG island methylation detection 2

Project description:Methylation of CpG islands associated with genes can affect the expression of the proximal gene, and methylation of non associated CpG islands correlates to genomic instability. This epigenetic modification has been shown to be important in many pathologies, from development and disease to cancer. We report the development of a novel high-resolution microarray that detects the methylation status of over 25,000 CpG islands in the human genome. Experiments were performed to demonstrate low system noise in the methodology and that the array probes have a high signal to noise ratio. Methylation measurements between different cell lines were validated demonstrating the accuracy of measurement. We then identified alterations in CpG islands, both those associated with gene promoters, as well as non-promoter associated islands in a set of breast and ovarian tumors. We demonstrate that this methodology accurately identifies methylation profiles in cancer and in principle it can differentiate any CpG methylation alterations and can be adapted to analyze other species. We have developed a method to profile genome wide methylation. 7 ovarian normal samples and 11 tumor samples from other individuals were analyzed for CpG methylation. After inter array normalization, the tumor samples were taken together and the methylation compared to that of the normal samples to identify regions of the CpG islands that are significantly altered between the two datasets. Some of these regions were validated for their methylation as a proof of principle for the method.

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Germline DNA Methylation Associated with Breast Cancer Predisposition

Project description:<p>Understanding and explaining hereditary predisposition to cancer has focused on the genetic etiology of the disease. However, mutations in known genes associated with breast cancer such as BRCA1 and BRCA2 account for less than 25% of familial cases of breast cancer. Heritable epigenetic modifications, in the form of hypermethylated MLH1 promoter alleles, have recently been shown to promote hereditary nonpolyposis colorectal cancer. We investigated the potential for an epigenetic basis for hereditary breast cancer by performing deep bisulfite sequencing of CpG islands and known promoter regions in germline DNA from 100 familial or early-onset breast or ovarian cancer patients.</p>

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Prediagnostic breast milk DNA methylation alterations in women who develop breast cancer

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2022-02-16 | PXD021821 | Pride

Genome wide DNA methylation sequencing by XmaI-RRBS resolves breast cancer epigenetic heterogeneity and suggests novel perspectives for personalized therapy

Project description:Aim: To provide a breast cancer (BC) methylotype classification by genome-wide CpG islands bisulfite DNA sequencing. Results: Overall, 6 distinct BC methylotypes were identified. Of these, BC cell lines constitute a separate group extremely highly methylated at the CpG islands. In turn, primary BC samples segregate into two major subtypes, highly and moderately methylated.

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DNA hypermethylation encroachment at CpG island borders in cancer is predisposed by H3K4 monomethylation [WGBS_Hs]

Project description:DNA methylation plays a key role in demarcation of regulatory regions, including promoter-associated CpG islands. While CpG islands are typically maintained in an unmethylated state in normal cells, a proportion of CpG islands are subject to hypermethylation in cancer cells. It still remains elusive how the exquisite demarcation of the bimodal methylation state is established and maintained at the CpG island flanks and conversely what triggers the erosion of CpG island DNA methylation in tumorigenesis. Here, we applied whole-genome bisulphite sequencing to study the comprehensive methylation patterns of prostate normal and cancer tissues. Alongside we performed TET-assisted bisulphite sequencing to study genome-wide DNA hydroxymethylation patterns of normal prostate and prostate cancer tissues.

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DNA hypermethylation encroachment at CpG island borders in cancer is predisposed by H3K4 monomethylation [TAB-Seq]

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