Circulating tumor cells capture disease evolution in advanced prostate cancer

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Advanced prostate cancer genetic analysis is hindered by limited, invasive tissue biopsies.
• Prostate cancer exhibits temporal genomic heterogeneity, necessitating repeated molecular profiling.
• Circulating tumor cells (CTCs) present a promising liquid biopsy alternative, but single-cell sequencing is challenging.

Purpose of the Study:

• To compare the genetic landscape of advanced prostate cancer using matched tumor tissue and pooled CTCs.
• To evaluate the utility of pooled CTCs for capturing tumor evolution and heterogeneity.

Main Methods:

• Exome sequencing was performed on matched treatment-naïve tumor tissue, castrate-resistant tumor tissue, and pooled CTC samples.
• Mutations identified in each sample type were compared to assess genomic concordance and divergence.

Main Results:

• 37% of CTC mutations were unique to CTCs, while 62% were shared with castrate-resistant disease.
• An acquired RB1 nonsense mutation, linked to small cell prostate cancer, was found in castrate-resistant and CTC samples.
• Genomic findings correlated with the tumor's transition to neuroendocrine features and altered therapy.

Conclusions:

• Pooled CTCs are effective for genetic analysis in late-stage prostate cancer.
• Liquid biopsies using CTCs can track tumor evolution and inform treatment strategies.