Single CpG methylation of Wnt signalling pathway components as a potential epigenetic marker of breast cancer

Background. Aberrant alterations of DNA methylation patterns in tumour cells are recognised as cancer-specific markers with high potential for clinical applications. Breast cancers represent one of the most common malignancies, what necessitates the development of molecular biomarkers to improve their diagnostics. Aim. Current work aimed at DNA methylation profiling of Wnt signalling pathway components SFRP2, PYGO1 and WIF1 and testing the biomarker potential for the detection of breast cancer specimens. Materials and Methods. Bisulfite pyrosequencing was employed for DNA methylation profiling in the vicinity of transcription start sites of the candidate genes. Analytical sensitivity and specificity of cancer detection were calculated using ROC curve analysis and SPSS software package. Results. In the breast cancer specimens, DNA hypermethylation was detected within the explored regions of SFRP2 , PYGO1 and WIF1 that included 14, 5 and 7 CpG-sites, respectively. Generally, a significantly higher methylation degree was found in the cancer specimens than in the histologically normal control tissue. High sensitivity and specificity of cancer detection was achieved when considering the methylation percentages of most informative single CpG-sites as potential biomarkers, namely 88% and 94% ( SFRP2 , hereafter: sensitivity and specificity), 100% and 81% ( PYGO1 ), 81% and 88% ( WIF1 ). No significant difference in the DNA methylation degree was detected at different stages of breast cancer suggesting an early onset of aberrant DNA hypermethylation. Conclusions. Breast cancer specimens can be accurately detected by analysing the methylation degrees of single CpG-sites of the explored genes, which are of interest as potential diagnostic markers. Identification of aberrant DNA hypermethylation pattern already at the early stages of tumour progression holds promise in the context of developing epigenetics-based early diagnostics.

метилирование ДНК, CpG-динуклеотиды, эпигенетические биомаркеры, злокачественные новообразования молочной железы, бисульфитное пиросеквенирование, DNA methylation, CpG-sites, epigenetic biomarkers, breast cancer, bisulfite pyrosequencing

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