Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer

The widespread and long-term use of potent therapies designed to repress androgen receptor (AR) signaling is changing the molecular and phenotypic landscapes of prostate cancer. We conducted molecular profiling of metastatic castration-resistant prostate cancer (mCRPC) patient specimens and patient-derived xenograft models and identified five distinct mCRPC phenotypes. Herein, we characterize an AR-low phenotype that has low AR expression with concomitant decreases in a subset of AR regulated genes, and an amphicrine phenotype that has both AR and neuroendocrine activity in the same cell. Furthermore, our data highlight an emerging squamous cell mCRPC phenotype. RNA sequencing of human prostate tumor cell lines, patient-derived xenograft (PDX) models, and metastatic castration-resistant prostate cancer (mCRPC) tumors using Illumina TruSeq Library prep and sequenced on Illumina HiSeq 2500. This series includes re-analyzed samples from GSE118435.