Rapid, Ultra-Low Coverage Copy Number Profiling Of Cell-Free Dna As A Precision Oncology Screening Strategy In Metastatic Castration-Resistant Prostate Cancer (Mcrpc).

144Background: Although cell free DNA (cfDNA) profiling by next generation sequencing (NGS) holds great promise for precision oncology, the inability to estimate tumor content a priori typically results in ultra-deep sequencing (e.g. 10,000x) based approaches—often at limited loci—to ensure accurate assessment of cfDNA samples where tumor content can be u003c 0.1%. However, a large subset of patients with advanced cancers, where most precision oncology is applied, have much greater cfDNA tumor content. Methods: Here we demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) on benchtop sequencers as a precision medicine screening strategy based on ultra-low coverage (~0.005x) tumor content determination through genome-wide copy number alteration (CNA) profiling using 48 plasma cfDNA samples from patients with advanced cancer. Results: Using this approach, we identified therapeutically relevant focal CNAs in 13 of 48 (27%) cfDNA samples from patients with metast...