Evaluating Liquid Biopsies for Methylomic Profiling of Prostate Cancer

Liquid biopsies offer significant potential for informing on cancer progression and therapeutic resistance via minimally invasive serial monitoring of genetic alterations. Although the cancer epigenome is a central driving force in most neoplasia, how well the tumour methylome can be monitored via liquid biopsies is relatively unknown. In this first of its kind study we made a direct comparison of two liquid biopsies: urine and blood, asking how well they represent the tumor methylome. Utilizing the Infinium Methylation EPIC BeadChip, we profiled DNA methylation in tissue, urine sediment and cell-free circulating DNA from four men with advanced stage prostate cancer. We show that both urine and plasma are viable surrogates for tumor tissue biopsies, capturing 78.63 and 62.21% of tumor-specific methylation alterations, respectively. We conclude that urine is an easily accessible and sensitive biofluid for the study of prostate cancer epigenomic alterations. Four patients, each with Tumour, Matched Normal, Urine Sediment and Plasma samples (n=16 total)