Dynamics of the cell-free DNA methylome of metastatic prostate cancer during androgen-targeting treatment

Madonna R Peter, Misha Bilenky, Ruth Isserlin, Gary D Bader, Shu Yi Shen, Daniel D De Carvalho, Aaron R Hansen, Pingzhao Hu, Neil E Fleshner, Anthony M Joshua, Martin Hirst, Bharati Bapat
Epigenomics 2020 September 1
Aim: We examined methylation changes in cell-free DNA (cfDNA) in metastatic castration-resistant prostate cancer (mCRPC) during treatment. Patients & methods: Genome-wide methylation analysis of sequentially collected cfDNA samples derived from mCRPC patients undergoing androgen-targeting therapy was performed. Results: Alterations in methylation states of genes previously implicated in prostate cancer progression were observed and patients that maintained methylation changes throughout therapy tended to have a longer time to clinical progression. Importantly, we also report that markers associated with a highly aggressive form of the disease, neuroendocrine-CRPC, were associated with a faster time to clinical progression. Conclusion: Our findings highlight the potential of monitoring the cfDNA methylome during therapy in mCRPC, which may serve as predictive markers of response to androgen-targeting agents.

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