Tracking breast cancer progression using Methylscape

Abstract

Cancer progression is intricately driven by epigenetic reprogramming, where aberrant DNA methylation patterns reshape gene regulation and cellular phenotypes. These alterations include promoter hypermethylation of tumour suppressor genes and global hypomethylation, collectively fuelling oncogenesis and disease advancement. We previously introduced the Methylscape--a distinct cancer-specific DNA methylation landscape characterized by clustered promoter hypermethylation and gene body hypomethylation--that enhances DNAs physical affinity for gold surfaces. In this study, we demonstrate that Methylscape can be leveraged to monitor cancer progression. Using a breast cancer epithelial-mesenchymal transition (EMT) model, we observe an increase in Methylscape enrichment of mesenchymal-state DNA during EMT, suggesting that this method can sensitively detect subtle epigenetic remodelling linked to tumour progression. Using a gold-based DNA desorption enrichment strategy coupled with methylation sequencing and qPCR, we show that hypermethylated regions are preferentially enriched. Finally, we developed a low-cost, disposable screen-printed electrode platform for stage-specific breast cancer monitoring. Together, these findings establish Methylscape as a promising biophysical biomarker for non-invasive and real-time monitoring of cancer progression, advancing its potential for clinical translation.