Comparison of Circulating Tumor DNA and Metastatic Tissue Biopsy in Identifying Mutations in Prostate Cancer

Key Points

  • In patients with evaluable ctDNA, all somatic mutations found in matched solid biopsies were identified in ctDNA.
  • Several patients had driver mutations in ctDNA that were not found in matched solid biopsy.

In a study reported in the Journal of the National Cancer Institute, Wyatt et al found high agreement between driver mutations in plasma circulating tumor DNA (ctDNA) and metastatic tissue biopsy in castration-resistant prostate cancer.

Mutations Identified in ctDNA

In the study, targeted sequencing for 72 clinically relevant genes was performed in 45 plasma cell–free DNA (cfDNA) samples obtained at biopsy of metastatic tissue. Among cfDNA samples, 34 (75.6%) had a ctDNA proportion greater than 2% of total cfDNA. Among these 34 patients, all somatic mutations in the matched metastatic tissue biopsies were present in ctDNA. Alterations in the 34 samples included AR amplification in 22 (64.7%); SPOP mutation in 3 (8.8%); and inactivating alterations in the tumor suppressors TP53, PTEN, RB1, APC, CDKN1B, BRCA2, and PIK3R1.

Copy number profiles of the matched liquid and solid biopsies were highly correlated, with a concordance of 88.9% being observed for individual gene copy number calls across clinically actionable genes (AR, BRCA2, ATM, PTEN, PIK3CA, PIK3CB, PIK3R1, TP53, and RB1). ctDNA sequencing robustly identified seven somatic mutations not found in solid biopsy; all were protein-altering mutations, and four were known cancer drivers, consisting of TP53 missense, RB1 frameshift, PTEN frameshift, and APC stopgain mutations.

The investigators concluded: “Our study shows that, in the majority of patients, a ctDNA assay is sufficient to identify all driver DNA alterations present in matched metastatic tissue and supports development of DNA biomarkers to guide [metastatic castration-resistant prostate cancer] patient management based on ctDNA alone.”

The study was supported by a Stand Up to Cancer Prostate Cancer Foundation Prostate Dream Team Translational Cancer Research Grant, Prostate Cancer Canada, and others.

Martin Gleave, MD, and Alexander Wyatt, DPhil, of Vancouver Prostate Centre, University of British Columbia, are the corresponding authors of the Journal of the National Cancer Institute article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.




By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.