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Identification and characterization of locus-specific methylation patterns within novel loci undergoing hypermethylation during breast cancer pathogenesis.

ABSTRACT: INTRODUCTION: Despite similar clinical and pathological features, large numbers of breast cancer patients experience different outcomes of the disease. This, together with the fact that the incidence of breast cancer is growing worldwide, emphasizes an urgent need for identification of new biomarkers for early cancer detection and stratification of patients. METHODS: We used ultrahigh-resolution microarrays to compare genomewide methylation patterns of breast carcinomas (n = 20) and nonmalignant breast tissue (n = 5). Biomarker properties of a subset of discovered differentially methylated regions (DMRs) were validated using methylation-sensitive high-resolution melting (MS-HRM) in a case-control study on a panel of breast carcinomas (n = 275) and non-malignant controls (n = 74). RESULTS: On the basis of microarray results, we selected 19 DMRs for large-scale screening of cases and controls. Analysis of the screening results showed that all DMRs tested displayed significant gains of methylation in the cancer tissue compared to the levels in control tissue. Interestingly, we observed two types of locus-specific methylation, with loci undergoing either predominantly full or heterogeneous methylation during carcinogenesis. Almost all tested DMRs (17 of 19) displayed low-level methylation in nonmalignant breast tissue, independently of locus-specific methylation patterns in cases. CONCLUSIONS: Specific loci can undergo either heterogeneous or full methylation during carcinogenesis, and loci hypermethylated in cancer frequently show low-level methylation in nonmalignant tissue.

SUBMITTER: Wojdacz TK

PROVIDER: S-EPMC3978461 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Identification and characterization of locus-specific methylation patterns within novel loci undergoing hypermethylation during breast cancer pathogenesis.

Wojdacz Tomasz K TK Windeløv Johanne A JA Thestrup Britta B BB Damsgaard Tine E TE Overgaard Jens J Hansen Lise L

Breast cancer research : BCR 20140203 1

<h4>Introduction</h4>Despite similar clinical and pathological features, large numbers of breast cancer patients experience different outcomes of the disease. This, together with the fact that the incidence of breast cancer is growing worldwide, emphasizes an urgent need for identification of new biomarkers for early cancer detection and stratification of patients.<h4>Methods</h4>We used ultrahigh-resolution microarrays to compare genomewide methylation patterns of breast carcinomas (n = 20) and ...[more]

PMID: 24490656

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Project description:BackgroundDNA methylation is an epigenetic event that may regulate gene expression. Because of this regulation role, aberrant DNA methylation is often associated with many diseases. Within-sample DNA co-methylation is the similarity of methylation in nearby cytosine sites of a chromosome. It is important to study co-methylation patterns. However, it is not well studied yet, and it is unclear to us what co-methylation patterns normal DNA samples have. Are the co-methylation patterns of the same tissue across several samples different? Are the co-methylation patterns of various tissues of the same sample different? To answer these questions, we conduct analyses using two sets of data: 3-sample-1-tissue (3S1T) and 1-sample-8-tissue (1S8T).ResultsTo study the co-methylation patterns of the two datasets, 3S1T and 1S8T, we investigate the following questions: How often does one methylation state change to other methylation states and how is this change associated with chromosome distance? Based on the 3S1T data, we find there is not significant co-methylation difference among the same spleen tissues of three different samples. However, the analysis results of 1S8T data show that there were significant differences among eight tissues of one sample. For both 3S1T and 1S8T data, we find that the no/low methylation state A and high/full methylation state D tend to remain the same along a chromosome region. We also find that the low/partial methylation state B and partial/high methylation state C tend to change to higher methylation states along a chromosome. Finally, we find that lengths of most co-methylation regions are very short with only a few hundred base pairs. In fact, only a small proportion of methylated regions are longer than 1000 base pairs.ConclusionsIn this paper, we have addressed a few questions regarding within-sample co-methylation patterns in normal tissues. Our statistical analysis results and answers may help researchers to better understand the biological process of DNA methylation. This may pave the way to develop better analysis methods for future methylation research.

Dataset Information

Identification and characterization of locus-specific methylation patterns within novel loci undergoing hypermethylation during breast cancer pathogenesis.

Publications

Identification and characterization of locus-specific methylation patterns within novel loci undergoing hypermethylation during breast cancer pathogenesis.

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