Liquid biopsies provide a non-invasive way to detect, diagnose and monitor cancers. Efforts so far have mostly focused on using genomic features of the tumor from cell-free DNA but, although these strategies can be useful, they fail to capture information about gene expression or chromatin accessibility, which can provide clinically relevant information about the primary site or histological subtype. To address this issue, Baca et al. developed a method to survey a variety of epigenetic features from 1 ml of plasma taken from 433 individuals with advanced disease or with no cancer history. Their samples — comprising 15 different types of cancer — were profiled using an immunoprecipitation-based approach to detect both DNA methylation and histone modifications (H3K4me3, H3K27ac and panH3ac). This choice of epigenetic marks provided information about enhancer activity, promoters and DNA methylation — all important determinants of gene expression and cellular states. The technique offered insight into the transcriptional state of the tumor, enabling the authors to identify expression of drug targets or biomarkers for diagnosis or treatment choice. Analysis of enhancer activity highlighted disease-relevant transcription factors — potential targets for tomorrow’s drugs — together with epigenetic drivers of treatment resistance and disease progression. This proof-of-principle study showcases the potential power of epigenetic profiling to provide actionable information in a clinically amenable way. The authors look forward to applying their technique to longitudinal samples, enabling the real-time monitoring of disease progression.
Original reference: Nat. Med. https://doi.org/10.1038/s41591-023-02605-z (2023)
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