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


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.

SUBMITTER: Lohr JG 

PROVIDER: S-EPMC4034575 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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

Lohr Jens G JG   Adalsteinsson Viktor A VA   Cibulskis Kristian K   Choudhury Atish D AD   Rosenberg Mara M   Cruz-Gordillo Peter P   Francis Joshua M JM   Zhang Cheng-Zhong CZ   Shalek Alex K AK   Satija Rahul R   Trombetta John J JJ   Lu Diana D   Tallapragada Naren N   Tahirova Narmin N   Kim Sora S   Blumenstiel Brendan B   Sougnez Carrie C   Lowe Alarice A   Wong Bang B   Auclair Daniel D   Van Allen Eliezer M EM   Nakabayashi Mari M   Lis Rosina T RT   Lee Gwo-Shu M GS   Li Tiantian T   Chabot Matthew S MS   Ly Amy A   Taplin Mary-Ellen ME   Clancy Thomas E TE   Loda Massimo M   Regev Aviv A   Meyerson Matthew M   Hahn William C WC   Kantoff Philip W PW   Golub Todd R TR   Getz Gad G   Boehm Jesse S JS   Love J Christopher JC  

Nature biotechnology 20140420 5


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  ...[more]

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