Investig Clin Urol.  2021 Mar;62(2):224-232. 10.4111/icu.20200406.

Genomic mutation profiling using liquid biopsy in Korean patients with prostate cancer: Circulating tumor DNA mutation predicts the development of castration resistance

Affiliations
  • 1Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 2Green Cross Genome, Yongin, Korea.
  • 3Department of Urology, VHS Medical Center, Seoul, Korea.
  • 4Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
  • 5Department of Bioinformatics, Soongsil University, Seoul, Korea

Abstract

Purpose
To investigate germline and somatic mutation profiles in Korean patients with prostate cancer using liquid biopsy and solid tissue testing and to evaluate the prognostic value of circulating tumor DNA (ctDNA) in predicting castration resistance in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
Materials and Methods
Plasma samples from 56 prostate cancer patients were subjected to next-generation sequencing (NGS) to identify germline mutations and ctDNA analysis using liquid biopsy to detect somatic mutations. Additionally, paired solid cancer tissues from 18 patients were subject to NGS to detect somatic mutations. The clinical parameters and ctDNA profiles of patients with mHSPC were analyzed to evaluate the prognostic value of ctDNA mutations with respect to predicting castration resistance using Cox proportional hazards regression analysis.
Results
Germline mutations occurred in 3.6% of the patients in this cohort, with mutations identified in RAD50 (1.8%) and BRCA1 (1.8%). Somatic mutations detected by liquid biopsy and solid tissue testing were common in TP53 (12.5%), PIK3CA (3.6%), and TMPRSS2-ERG (3.6%). Of the 18 patients with paired tissue testing, two patients had at least one identical somatic mutation in both the liquid biopsy and solid tissue testing. In patients with mHSPC, the presence of ctDNA mutations could independently predict the castration resistance development (hazard ratio, 13.048; 95% confidential interval, 1.109–153.505; p=0.041).
Conclusions
Korean patients with prostate cancer showed a relatively low germline mutation rate compared to other ethnicities. The ctDNA mutations detected by liquid biopsy can predict the development of castration resistance in patients with mHSPC.

Keyword

Biomarkers; Circulating tumor DNA; Prostatic neoplasms; Prostatic neoplasms; castration-resistant
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