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 AuclairEliezer 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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)479-484
Number of pages6
JournalNature Biotechnology
Volume32
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Exome
Circulating Neoplastic Cells
Tumors
Prostatic Neoplasms
Cells
Neoplasms
Mutation
Censuses
Genomics
Tissue
Oncology
Lymph Nodes
Genome
Neoplasm Metastasis
Genes

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Biotechnology
  • Molecular Medicine
  • Bioengineering
  • Biomedical Engineering

Cite this

Lohr, J. G., Adalsteinsson, V. A., Cibulskis, K., Choudhury, A. D., Rosenberg, M., Cruz-Gordillo, P., ... Love, J. C. (2014). Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nature Biotechnology, 32(5), 479-484. https://doi.org/10.1038/nbt.2892

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

In: Nature Biotechnology, Vol. 32, No. 5, 2014, p. 479-484.

Research output: Contribution to journalArticle

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, GSM, Li, T, Chabot, MS, Ly, A, Taplin, ME, Clancy, TE, Loda, M, Regev, A, Meyerson, M, Hahn, WC, Kantoff, PW, Golub, TR, Getz, G, Boehm, JS & Love, JC 2014, 'Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer', Nature Biotechnology, vol. 32, no. 5, pp. 479-484. https://doi.org/10.1038/nbt.2892
Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M, Cruz-Gordillo P et al. Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nature Biotechnology. 2014;32(5):479-484. https://doi.org/10.1038/nbt.2892
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. / Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. In: Nature Biotechnology. 2014 ; Vol. 32, No. 5. pp. 479-484.
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AU - Cruz-Gordillo, Peter

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AU - Zhang, Cheng Zhong

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AU - Trombetta, John J.

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AU - Sougnez, Carrie

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AU - Meyerson, Matthew

AU - Hahn, William C.

AU - Kantoff, Philip W.

AU - Golub, Todd R.

AU - Getz, Gad

AU - Boehm, Jesse S.

AU - Love, J. Christopher

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