Molecular and clinical implications of CHD1 loss and SPOP mutations in advanced prostate cancer.

5064Background: CHD1 deletions (CHD1del) and SPOP mutations (SPOPmut) frequently co-occur in prostate cancer (PCa) with lower frequencies observed in castration-resistant PCa (CRPC). Responses to standard treatments in this subset of patients have not been previously reported. We studied the molecular and clinical characteristics of CHD1del/SPOPmut metastatic CRPC (mCRPC) analyzing CHD1 presence/loss during disease progression and correlation to response to Abiraterone acetate (AA). Methods: We identified mCRPC patients who had hormone naive (HNPC) and CRPC tumor samples available: these were analyzed for CHD1, PTEN and ERG expression by immunohistochemistry (IHC). SPOP status was determined by targeted next generation sequencing (NGS). Correlations with CHD1/SPOP status and clinical outcomes and responses to AA were analysed using Cox-regression and Log-Rank analyses. Results: Tumor samples from 89 patients who had progressed from HNPC to CRPC were analyzed in a cohort enriched for SPOPmut. CHD1 protein ...