TY - JOUR

T1 - Identification and characterization of locus specific methylation patterns within novel loci undergoing hypermethylation during breast cancer pathogenesis

AU - Wojdacz, Tomasz K

AU - Windeløv, Johanne Agerlin

AU - Thestrup, Britta B

AU - Damsgaard, Tine E

AU - Overgaard, Jens

AU - Hansen, Lise Lotte

PY - 2014/2/3

Y1 - 2014/2/3

N2 - 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 ultra high-resolution microarrays to compare genome-wide methylation patterns of breast carcinomas (N = 20) and non-malignant breast tissue (N = 5). Biomarker properties of a subset of discovered differentially methylated regions (DMRs) was 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: Based on 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 when compared to the levels in control tissue. Interestingly, we have observed two types of locus specific methylation, with loci undergoing either predominantly full or heterogeneous methylation during carcinogenesis. At the same time almost all tested DMRs (17 out of 19) displayed low-level methylation in non-malignant breast tissue independent of locus specific methylation pattern 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 non-malignant tissue.

AB - 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 ultra high-resolution microarrays to compare genome-wide methylation patterns of breast carcinomas (N = 20) and non-malignant breast tissue (N = 5). Biomarker properties of a subset of discovered differentially methylated regions (DMRs) was 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: Based on 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 when compared to the levels in control tissue. Interestingly, we have observed two types of locus specific methylation, with loci undergoing either predominantly full or heterogeneous methylation during carcinogenesis. At the same time almost all tested DMRs (17 out of 19) displayed low-level methylation in non-malignant breast tissue independent of locus specific methylation pattern 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 non-malignant tissue.

U2 - 10.1186/bcr3612

DO - 10.1186/bcr3612

M3 - Journal article

C2 - 24490656

VL - 16

SP - 1

EP - 10

JO - Breast Cancer Research

JF - Breast Cancer Research

SN - 1465-5411

IS - 1

M1 - R17

ER -