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Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer.
|Publication Type||Journal Article|
|Authors||Lohr, JG, Adalsteinsson VA, Cibulskis K., Choudhury AD, Rosenberg M., Cruz-Gordillo P., Francis JM, Zhang CZ, Shalek AK, Satija R., Trombetta JJ, Lu D., Tallapragada N., Tahirova N., Kim S., Blumenstiel B., Sougnez C., Lowe A., Wong B., Auclair D., Van Allen EM, Nakabayashi M., Lis RT, Lee GS, Li T., Chabot MS, Ly A., Taplin ME, Clancy TE, Loda M., Regev A., Meyerson M., Hahn WC, Kantoff PW, Golub T. R., Getz G., Boehm JS, and Love JC|
|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.|
|Year of Publication||2014|
|Date Published (YYYY/MM/DD)||2014/05/01|