Dynamics of the cell-free DNA methylome of metastatic prostate cancer during androgen-targeting treatment
Aim: We examined methylation changes in cell-free DNA (cfDNA) in metastatic castration resistant prostate cancer (mCRPC) during treatment. Patients and 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 (TTP). Importantly, we also report that markers associated with a highly aggressive form of the disease, Neuroendocrine-CRPC, were associated with a faster TTP. 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. Overall design: We performed methylated DNA immunoprecipitation followed by high-throughput sequencing (cfMeDIP-seq) of cfDNA derived from 16 patients with mCRPC at various stages of treatment with androgen-targerting agents. Visit A = Baseline/pre-treatment visit; Visit B = Week-12 (+/- 2 weeks) during treatment; Visit C = Clinical progression/change of treatment. Each cfDNA sample has a methylated DNA enriched sequencing file and an input control file.