Epigenome-Wide DNA Methylation Profiling of Matched Primary Breast Cancers and Brain Metastases Reveals Epigenetic Markers linked to Metastatic Progression: A Preliminary Study

Abstract

Introduction Breast cancer represents the most prevalent malignancy among women globally, with a rising incidence of metastases to the central nervous system. The presence of brain metastases is associated with a poor prognosis, largely due to the limited availability of effective treatment modalities. Methods In this preliminary study, we performed an epigenome-wide DNA-methylation analysis of matched primary breast cancer and brain metastasis of the same patients applying the Illumina Infinium EPIC Bead Chip interrogating more than 850,000 CpG sites at single base resolution. Results We found that primary breast cancers and corresponding metastases are very similar on the global DNA methylation level. Detailed analysis showed aberrant methylation patterns that reflect the process of brain metastasis. We identified 107 nominally significant methylated CpG sites (DMCGs) within promoter and gene regions (Δβ ≥ 0.1, p-value < 0.05), when comparing primary breast tumors to their brain metastatic counterparts. However, due to the limited sample size, no individual CpG site retained statistically significant after correction for multiple testing. Conclusion Our study highlights specific aberrant DNA methylation patterns that are associated with brain metastasis in breast cancer. Characterizing these epigenetic alterations provides a promising avenue for identifying novel therapeutic targets and clinically relevant biomarkers.