Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

DNA methylation profiling of ductal carcinoma in situ (DCIS)

ABSTRACT: 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 Methylation patterns of tumors; six patients with early stage breast cancer (DCIS)

ORGANISM(S): Homo sapiens

SUBMITTER: Stella Tommasi

PROVIDER: E-GEOD-14865 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Methylation of homeobox genes is a frequent and early epigenetic event in breast cancer.

Tommasi Stella S Karm Deborah L DL Wu Xiwei X Yen Yun Y Pfeifer Gerd P GP

Breast cancer research : BCR 20090227 1

<h4>Introduction</h4>Aberrant methylation of CpG islands is a hallmark of cancer and occurs at an early stage in breast tumorigenesis. However, its impact on tumor development is not fully determined, and its potential as a diagnostic biomarker remains to be validated. Methylation profiling of invasive breast carcinoma has been largely explored. Conversely, very little and sparse information is available on early-stage breast cancer. To gain insight into the epigenetic switches that may promote ...[more]

PMID: 19250546

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Project description:Using glutathione peroxidase, Gpx1 and Gpx2, double knockout (Gpx1/2-KO) mice as a model of inflammatory bowel disease predisposing to intestinal cancer, we analyzed genome-wide DNA methylation and chromatin changingM-bM-^@M-^Ys in the mouse ileum during chronic inflammation, aging and cancer. We found that inflammation leads to aberrant DNA methylation in Polycomb target genes, with 70% of the ~250 genes methylated in the inflamed tissue being PcG targets in embryonic stem cells and 58% of the methylated genes being marked by H3K27 trimethylation in the ileum of adult wildtype mice. Acquisition of DNA methylation at CpG islands in the ileum of Gpx-1/2-KO mice frequently correlated with loss of H3K27 trimethylation at the same loci. Inflammation-associated DNA methylation occurs preferentially in tissue-specific silent genes and, importantly, is much more frequently represented in tumors than is age-dependent DNA methylation. 60% of aberrant methylation found in tumors is also present in the inflamed tissue. In summary, inflammation creates a signature of aberrant DNA methylation, which is observed later in the malignant tissue and is directed by the PcG complex. In our study we used mice Gpx1/2-ko with B6 and B6.129 genetic background which are characterized by different level of inflammation in ileum and different tumor susceptibility. DNA methylation was analyzed by using MIRA-assisted Microarrays approach. Changing of the DNA methylation in intestinal epithelium during inflammation and tumorgenesis in Gpx1/2-KO mice were compared to healthy control mice with matching age. Aged dependent DNA methylation was study by comparing DNA methylation between 28-days-old healthy control mice with 8-month-old mice. To detect DKO-specific DNA methylation, we compared the changing DNA methylation in liver from Gpx1/2-KO mice with liver from control mice at age 28 days and 8 month. Association of the inflammation dependent DNA methylation with Polycomb targets and loss of H3K27me3 were verified by ChIp-on-ChIp experiments using H3K27me3 antibodies.

Dataset Information

DNA methylation profiling of ductal carcinoma in situ (DCIS)

Publications

Methylation of homeobox genes is a frequent and early epigenetic event in breast cancer.

Similar Datasets

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