Dynamics of the cell-free DNA methylome of metastatic prostate cancer during androgen-targeting treatment
M. R. Peter, M. Bilenky, R. Isserlin, G. D. Bader, S. Y. Shen, D. D. De Carvalho, A. R. Hansen, P. Hu, N. E. Fleshner, A. M. Joshua, M. Hirst, B. Bapat
Abstract
AimWe examined methylation changes in cell-free DNA (cfDNA) in metastatic castration resistant prostate cancer (mCRPC) during treatment. Materials and MethodsGenome-wide methylation analysis of sequentially collected cfDNA samples derived from mCRPC patients undergoing androgen-targeting therapy was performed. ResultsAlterations in methylation states 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. ConclusionOur findings highlight the potential of monitoring cfDNA methylome during therapy in mCRPC, which may serve as predictive markers of response to androgen-targeting agents.
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