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- Title
Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer.
- Authors
Lohr, Jens G; Adalsteinsson, Viktor A; Cibulskis, Kristian; Choudhury, Atish D; Rosenberg, Mara; Cruz-Gordillo, Peter; Francis, Joshua M; Zhang, Cheng-Zhong; Shalek, Alex K; Satija, Rahul; Trombetta, John J; Lu, Diana; Tallapragada, Naren; Tahirova, Narmin; Kim, Sora; Blumenstiel, Brendan; Sougnez, Carrie; Lowe, Alarice; Wong, Bang; Auclair, Daniel
- 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.
- Subjects
METASTASIS; PROSTATE cancer; PROSTATE cancer &; genetics; GENOMICS; GENE mapping
- Publication
Nature Biotechnology, 2014, Vol 32, Issue 5, p479
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/nbt.2892