Peer-reviewed
Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer
Jens G Lohr, Viktor A Adalsteinsson, Kristian Cibulskis, Atish D Choudhury, Mara Rosenberg, Peter Cruz-Gordillo, Joshua M Francis, Cheng-Zhong Zhang, Alex K Shalek, Rahul Satija, John J Trombetta, Diana Lu, Naren Tallapragada, Narmin Tahirova, Sora Kim, Brendan Blumenstiel, Carrie Sougnez, Alarice Lowe, Bang Wong, Daniel Auclair, Eliezer M Van Allen, Mari Nakabayashi, Rosina T Lis, Gwo-Shu M Lee, Tiantian Li, Matthew S Chabot, Amy Ly, Mary-Ellen Taplin, Thomas E Clancy, Massimo Loda, Aviv Regev, Matthew Meyerson, William C Hahn, Philip W Kantoff, Todd R Golub, Gad Getz, Jesse S Boehm, J Christopher Love
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
Article, 2014
Nature biotechnology, 32, 201405, 479
2014