Epigenomic profiling of circulating chromatin to detect and monitor squamous transformation in prostate cancer

Transformation to squamous cell carcinoma is a rare resistance mechanism in patients with advanced prostate cancer that impacts both prognosis and treatment. Herein, we profile circulating chromatin in serial plasma samples collected from a patient with metastatic prostate cancer that experienced squamous transformation. We detect dynamic changes in gene regulation from circulating chromatin reflecting the emergence of squamous differentiation, enabling non-invasive diagnosis and monitoring of this resistance phenotype. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone modifications H3K27ac and H3K4me3, and low pass whole genome sequencing on cell-free DNA.