Comparative Molecular Analyses of LNCaP and Substrains Identify Drivers of Cancer Behavior and Therapy Resistance [ATAC-seq]

Overall, the LNCaP line has served as a remarkably versatile PC model, though the molecular characteristics of several important substrains have not been established nor compared in a systematic manner. In this study, we used genome-scale approaches to characterize the genomic and transcriptomic features of the parental LNCaP_FGC line, and a spectrum of 12 derivative models that have been deployed for studies of PC. These studies provide insights into the biochemical features that endow PC with the potential to resist AR-directed therapy and identify features that may underlie the metastatic and treatment resistant phenotypes observed in patients. An important but under-appreciated feature of LNCaP concerns the remarkable heterogeneity of the original LNCaP isolate and the current LNCaP_FGC line which was never subjected to clonal selection. This feature, coupled with the inherent DNA mismatch repair deficiency and genomic instability, has produced a remarkable spectrum of sublines that have provided important insights into PC pathobiology, but also challenge reproducibility and the accurate interpretation of experimental findings. ATAC-Seq of LNCaP Sublines using OMNI-ATACseq protocol