Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer Academic Article uri icon

Overview

MeSH Major

  • Exome
  • Neoplastic Cells, Circulating
  • Prostatic Neoplasms

abstract

  • Comprehensive analyses of cancer genomes promise to inform prognoses and precise cancer treatments. A major barrier, however, is inaccessibility of metastatic tissue. A potential solution is to characterize circulating tumor cells (CTCs), but this requires overcoming the challenges of isolating rare cells and sequencing low-input material. Here we report an integrated process to isolate, qualify and sequence whole exomes of CTCs with high fidelity using a census-based sequencing strategy. Power calculations suggest that mapping of >99.995% of the standard exome is possible in CTCs. We validated our process in two patients with prostate cancer, including one for whom we sequenced CTCs, a lymph node metastasis and nine cores of the primary tumor. Fifty-one of 73 CTC mutations (70%) were present in matched tissue. Moreover, we identified 10 early trunk and 56 metastatic trunk mutations in the non-CTC tumor samples and found 90% and 73% of these mutations, respectively, in CTC exomes. This study establishes a foundation for CTC genomics in the clinic.

authors

publication date

  • January 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4034575

Digital Object Identifier (DOI)

  • 10.1038/nbt.2892

PubMed ID

  • 24752078

Additional Document Info

start page

  • 479

end page

  • 84

volume

  • 32

number

  • 5