Journal
NATURE BIOTECHNOLOGY
Volume 32, Issue 5, Pages 479-U202Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.2892
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Funding
- Conquer Cancer Foundation Young Investigator Award
- US National Institutes of Health (DF/HCC SPORE) [5P50CA100707-10]
- Wong Family Award
- National Science Foundation
- Prostate Cancer Foundation Young Investigator Award
- Department of Defense Physician Scientist Training Award
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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.
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