Circulating tumor cells capture disease evolution in advanced prostate cancer

Justin Lack, Marc Gillard, Maggie Cam, Gladell P. Paner, David J. VanderWeele*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: Genetic analysis of advanced cancer is limited by availability of representative tissue. Biopsies of prostate cancer metastasized to bone are invasive with low quantity of tumor tissue. The prostate cancer genome is dynamic, however, with temporal heterogeneity requiring repeated evaluation as the disease evolves. Circulating tumor cells (CTCs) offer an alternative, "liquid biopsy", though single CTC sequencing efforts are laborious with high failure rates. Methods: We performed exome sequencing of matched treatment-naïve tumor tissue, castrate resistant tumor tissue, and pooled CTC samples, and compared mutations identified in each. Results: Thirty-seven percent of CTC mutations were private to CTCs, one mutation was shared with treatment-naïve disease alone, and 62% of mutations were shared with castrate-resistant disease, either alone or with treatment-naïve disease. An acquired nonsense mutation in the Retinoblastoma gene, which is associated with progression to small cell cancer, was identified in castrate resistant and CTC samples, but not treatment-naïve disease. This timecourse correlated with the tumor acquiring neuroendocrine features and a change to neuroendocrine-specific therapy. Conclusions: These data support the use of pooled CTCs to facilitate the genetic analysis of late stage prostate cancer.

Original languageEnglish (US)
Article number44
JournalJournal of Translational Medicine
Volume15
Issue number1
DOIs
StatePublished - Feb 23 2017

Keywords

  • Castrate resistant prostate cancer
  • Circulating tumor cells
  • Neuroendocrine prostate cancer
  • Tumor evolution

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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