Targeted next-generation sequencing for locally advanced prostate cancer in the Korean population

This study aimed to evaluate the feasibility of pan-cancer panel analysis for locally advanced prostate cancer in the Korean population.

We analyzed 20 patients with locally advanced prostate cancer who underwent radical prostatectomy. A pan-cancer panel (1.9 Mbp) developed by Seoul National University Hospital (SNUH), composed of 183 target genes, 23 fusion genes, and 45 drug target regions was used for this analysis. We compared the SNUH pan-cancer panel results with The Cancer Genome Atlas (TCGA) database to search for different mutations in the Korean population. Clinical data were analyzed with univariate and multivariate analysis, and p-values <0.05 were considered statistically significant. Kaplan-Meier curve and log-rank tests were performed to evaluate survival.

The average age of the patients and initial prostate-specific antigen values were 69.3±7.8 years and 66.3±16.9 ng/dL, respectively. Average sequencing depth was 574.5±304.1×. Ninety-nine genetic mutations and 5 fusions were detected. SPOP (25%), KMT2D (20%), and BRAF (15%) were frequently detected. ERG fusions were recurrently detected in 20% of the patients, with SLMAP and SETD4 as novel fusion partners. BRAF mutation was frequently detected in this study, but not in the TCGA database. Multivariate analysis showed BRAF mutation as an independent prognostic factor for biochemical recurrence (hazard ratio, 9.84; p=0.03).

The pan-cancer panel comprising genes related to prostate cancer is a useful tool for evaluating genetic alterations in locally advanced prostate cancers. Our results suggest that the BRAF mutation is associated with biochemical recurrence in the Korean population.