Details

Autor(en) / Beteiligte

• 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
• Van Allen, Eliezer M
• Nakabayashi, Mari
• Lis, Rosina T
• Lee, Gwo-Shu M
• Li, Tiantian
• Chabot, Matthew S
• Ly, Amy
• Taplin, Mary-Ellen
• Clancy, Thomas E
• Loda, Massimo
• Regev, Aviv
• Meyerson, Matthew
• Hahn, William C
• Kantoff, Philip W
• Golub, Todd R
• Getz, Gad
• Boehm, Jesse S
• Love, J Christopher

Titel

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

Ist Teil von

• Nature biotechnology, 2014-05, Vol.32 (5), p.479-484

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• Whole-exome sequencing of circulating tumor cells enables accurate and powered calling of somatic point mutations. 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.