Whole exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer
Adalsteinsson, Viktor A.
Shalek, Alex K.
Trombetta, John T.
Lis, Rosina T.
Lee, Gwo-Shu M.
Chabot, Matthew S.
Boehm, Jesse S.
Love, J. ChristopherNote: Order does not necessarily reflect citation order of authors.
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CitationLohr, J. G., V. A. Adalsteinsson, K. Cibulskis, A. D. Choudhury, M. Rosenberg, P. Cruz-Gordillo, J. Francis, et al. 2014. “Whole exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer.” Nature biotechnology 32 (5): 479-484. doi:10.1038/nbt.2892. http://dx.doi.org/10.1038/nbt.2892.
AbstractComprehensive 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 prostate cancer patients 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 observed 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, respectively, in CTC exomes. This study establishes a foundation for CTC genomics in the clinic.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13454751
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