Identification and characterization of locus-specific methylation patterns within novel loci undergoing hypermethylation during breast cancer pathogenesis
| Autor: | Johanne Agerlin Windeløv, Tomasz K. Wojdacz, Lise Lotte Hansen, Tine Engberg Damsgaard, Britta B. Thestrup, Jens Overgaard |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Microarray
Breast Neoplasms Biology Bioinformatics medicine.disease_cause Epigenesis Genetic Breast cancer Surgical oncology medicine Biomarkers Tumor Humans Medicine(all) Base Sequence Methylation Sequence Analysis DNA DNA Methylation medicine.disease Differentially methylated regions Tissue Array Analysis Case-Control Studies DNA methylation Cancer research Biomarker (medicine) CpG Islands Female Carcinogenesis Research Article |
| Zdroj: | Breast Cancer Research : BCR Wojdacz, T K, Windeløv, J A, Thestrup, B B, Damsgaard, T E, Overgaard, J & Hansen, L L 2014, ' Identification and characterization of locus specific methylation patterns within novel loci undergoing hypermethylation during breast cancer pathogenesis ', Breast Cancer Research (Online Edition), vol. 16, R17 . https://doi.org/10.1186/bcr3612 |
| ISSN: | 1465-542X 1465-5411 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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