Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer.

Nat Biotechnol
Authors
Keywords
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.

Year of Publication
2014
Journal
Nat Biotechnol
Volume
32
Issue
5
Pages
479-84
Date Published
2014 May
ISSN
1546-1696
URL
DOI
10.1038/nbt.2892
PubMed ID
24752078
PubMed Central ID
PMC4034575
Links
Grant list
F32 HD075541 / HD / NICHD NIH HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
5P50CA100707-10 / CA / NCI NIH HHS / United States
P30-CA14051 / CA / NCI NIH HHS / United States
T32 CA009172 / CA / NCI NIH HHS / United States
P50 CA100707 / CA / NCI NIH HHS / United States