Multiomic assessments of LNCaP and derived cell strains reveal determinants of prostate cancer pathobiology (RNA-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. Overall design: RNA sequencing of LNCaP-FGC and 12 LNCaP sublines using Illumina stranded mRNA TruSeq Library prep and sequenced on Illumina NovaSeq 6000.