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J Transl Med. 2017 Feb 23;15(1):44. doi: 10.1186/s12967-017-1138-3.

Circulating tumor cells capture disease evolution in advanced prostate cancer.

Author information

1
Center for Cancer Research Collaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.
2
Department of Surgery, University of Chicago, Chicago, IL, 60615, USA.
3
Department of Pathology, University of Chicago, Chicago, IL, 60615, USA.
4
Laboratory for Genitourinary Pathogenesis, Center for Cancer Research, National Cancer Institute, 37 Convent Drive, Rm 1066A, Bethesda, MD, 20892, USA. david.vanderweele@nih.gov.
5
Department of Medicine, University of Chicago, Chicago, IL, 60615, USA. david.vanderweele@nih.gov.

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.

KEYWORDS:

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

PMID:
28228136
PMCID:
PMC5322599
DOI:
10.1186/s12967-017-1138-3
[Indexed for MEDLINE]
Free PMC Article

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