Integrative molecular analysis of DNA methylation dynamics unveils molecules with prognostic potential in breast cancer

DNA methylation acts as a major epigenetic modification in mammals, characterized by the transfer of a methyl group to a cytosine. DNA methylation plays pivotal role in regulating normal development and misregulation in cells leads to abnormal phenotype as is seen in several cancers. Any mutations or expression anomalies of genes encoding regulators of DNA methylation may lead to abnormal expression of critical molecules. A comprehensive genomic study encompassing all the genes related to DNA methylation regulation in relation to breast cancer is lacking. We used genomic and transcriptomic datasets from Pan-Cancer TCGA (The Cancer Genome Atlas), Genotype-Tissue Expression (GTEx) and microarray platforms and conducted in silico analysis of all the genes related to DNA methylation with respect to writing, reading, and erasing this epigenetic mark. cBioportal was employed for analysis of mutations while Xena and KMPlot were utilized for expression changes and patient survival, respectively.The molecular and genetic profile of genes related DNA methylation regulation identified multiple mutations and detected aberrant expression in breast cancer. While most of the genes were found to have relatively low mutation rates, the expression profiling showed significant differences between normal and disease tissues. In addition, deregulated expression of some of the genes, namely, DNMT3B, MBD1, MBD6, BAZ2B, ZBTB38, KLF4, TET2 andTDG was correlated with patient prognosis. The current study, to our best knowledge, is the first one that unravels a comprehensive molecular and genetic profile of DNA methylation machinery genes in breast cancer. This study will advance our understanding of the etiology of the disease and may serve for identification of alternative targets for novel therapeutic strategies in cancer.