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Nat Biotechnol. 2014 May;32(5):479-84. doi: 10.1038/nbt.2892. Epub 2014 Apr 20.

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

Author information

1
1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA. [4].
2
1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3].
3
1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2].
4
1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA.
5
The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
6
1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
7
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
8
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
9
Brigham and Women's Hospital, Boston, Massachusetts, USA.
10
1] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA.
11
Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
12
Massachusetts General Hospital, Boston, Massachusetts, USA.
13
1] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA. [3] Brigham and Women's Hospital, Boston, Massachusetts, USA.
14
1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA. [4] Brigham and Women's Hospital, Boston, Massachusetts, USA.
15
1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
16
1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA. [4] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
17
1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Massachusetts General Hospital, Boston, Massachusetts, USA.
18
1] The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.

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.

Comment in

PMID:
24752078
PMCID:
PMC4034575
DOI:
10.1038/nbt.2892
[Indexed for MEDLINE]
Free PMC Article

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