npj Precision Oncology (Aug 2021)

Circulating tumor cell heterogeneity in neuroendocrine prostate cancer by single cell copy number analysis

  • Vincenza Conteduca,
  • Sheng-Yu Ku,
  • Luisa Fernandez,
  • Angel Dago-Rodriquez,
  • Jerry Lee,
  • Adam Jendrisak,
  • Megan Slade,
  • Cole Gilbertson,
  • Jyothi Manohar,
  • Michael Sigouros,
  • Yipeng Wang,
  • Ryan Dittamore,
  • Rick Wenstrup,
  • Juan Miguel Mosquera,
  • Joseph D. Schonhoft,
  • Himisha Beltran

DOI
https://doi.org/10.1038/s41698-021-00211-1
Journal volume & issue
Vol. 5, no. 1
pp. 1 – 8

Abstract

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Abstract Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that may arise de novo or develop from pre-existing prostate adenocarcinoma as a mechanism of treatment resistance. The combined loss of tumor suppressors RB1, TP53, and PTEN are frequent in NEPC but also present in a subset of prostate adenocarcinomas. Most clinical and preclinical studies support a trans-differentiation process, whereby NEPC arises clonally from a prostate adenocarcinoma precursor during the course of treatment resistance. Here we highlight a case of NEPC with significant intra-patient heterogeneity observed across metastases. We further demonstrate how single-cell genomic analysis of circulating tumor cells combined with a phenotypic evaluation of cellular diversity can be considered as a window into tumor heterogeneity in patients with advanced prostate cancer.