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Nat Biotechnol DOI:10.1038/nbt.2892

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

Publication TypeJournal Article
Year of Publication2014
AuthorsLohr, JG, Adalsteinsson, VA, Cibulskis, K, Choudhury, AD, Rosenberg, M, Cruz-Gordillo, P, Francis, JM, Zhang, C-Z, 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, G-SM, Li, T, Chabot, MS, Ly, A, Taplin, M-E, Clancy, TE, Loda, M, Regev, A, Meyerson, M, Hahn, WC, Kantoff, PW, Golub, TR, Getz, G, Boehm, JS, J Love, C
JournalNat Biotechnol
Volume32
Issue5
Pages479-84
Date Published2014 May
ISSN1546-1696
KeywordsExome, Humans, Male, Mutation, Neoplastic Cells, Circulating, Prostatic Neoplasms
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.

URLhttp://dx.doi.org/10.1038/nbt.2892
DOI10.1038/nbt.2892
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24752078?dopt=Abstract

Alternate JournalNat. Biotechnol.
PubMed ID24752078
PubMed Central IDPMC4034575
Grant ListF32 HD075541 / HD / NICHD NIH HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
5P50CA100707-10 / CA / NCI NIH HHS / United States
P30-CA14051 / CA / NCI NIH HHS / United States
T32 CA009172 / CA / NCI NIH HHS / United States
P50 CA100707 / CA / NCI NIH HHS / United States