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 Auclair; Eliezer 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

doi:10.1038/nbt.2892

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

Biology and Genomics

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Pages (from-to)	479-484
Number of pages	6
Journal	Nature Biotechnology
Volume	32
Issue number	5
DOIs	https://doi.org/10.1038/nbt.2892
State	Published - May 2014

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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10.1038/nbt.2892

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Lohr, J. G., Adalsteinsson, V. A., Cibulskis, K., Choudhury, A. D., Rosenberg, M., Cruz-Gordillo, P., Francis, J. M., Zhang, C. Z., Shalek, A. K., Satija, R., Trombetta, J. J., Lu, D., Tallapragada, N., Tahirova, N., Kim, S., Blumenstiel, B., Sougnez, C., Lowe, A., Wong, B., ... 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

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

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title = "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.",

author = "Lohr, {Jens G.} and Adalsteinsson, {Viktor A.} and Kristian Cibulskis and Choudhury, {Atish D.} and Mara Rosenberg and Peter Cruz-Gordillo and Francis, {Joshua M.} and Zhang, {Cheng Zhong} and Shalek, {Alex K.} and Rahul Satija and Trombetta, {John J.} and Diana Lu and Naren Tallapragada and Narmin Tahirova and Sora Kim and Brendan Blumenstiel and Carrie Sougnez and Alarice Lowe and Bang Wong and Daniel Auclair and {Van Allen}, {Eliezer M.} and Mari Nakabayashi and Lis, {Rosina T.} and Lee, {Gwo Shu M.} and Tiantian Li and Chabot, {Matthew S.} and Amy Ly and Taplin, {Mary Ellen} and Clancy, {Thomas E.} and Massimo Loda and Aviv Regev and Matthew Meyerson and Hahn, {William C.} and Kantoff, {Philip W.} and Golub, {Todd R.} and Gad Getz and Boehm, {Jesse S.} and Love, {J. Christopher}",

year = "2014",

month = may,

doi = "10.1038/nbt.2892",

language = "English (US)",

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AU - Lohr, Jens G.

AU - Adalsteinsson, Viktor A.

AU - Cibulskis, Kristian

AU - Choudhury, Atish D.

AU - Rosenberg, Mara

AU - Cruz-Gordillo, Peter

AU - Francis, Joshua M.

AU - Zhang, Cheng Zhong

AU - Shalek, Alex K.

AU - Satija, Rahul

AU - Trombetta, John J.

AU - Lu, Diana

AU - Tallapragada, Naren

AU - Tahirova, Narmin

AU - Kim, Sora

AU - Blumenstiel, Brendan

AU - Sougnez, Carrie

AU - Lowe, Alarice

AU - Wong, Bang

AU - Auclair, Daniel

AU - Van Allen, Eliezer M.

AU - Nakabayashi, Mari

AU - Lis, Rosina T.

AU - Lee, Gwo Shu M.

AU - Li, Tiantian

AU - Chabot, Matthew S.

AU - Ly, Amy

AU - Taplin, Mary Ellen

AU - Clancy, Thomas E.

AU - Loda, Massimo

AU - Regev, Aviv

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

PY - 2014/5

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N2 - 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.

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

Abstract

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