Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer (original) (raw)

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Acknowledgements

J.G.L. was supported by a Conquer Cancer Foundation Young Investigator Award, US National Institutes of Health grant 5P50CA100707-10 (DF/HCC SPORE) and the Wong Family Award. V.A.A. was supported in part by a graduate fellowship from the National Science Foundation. A.D.C. is supported by the Prostate Cancer Foundation Young Investigator Award and the Department of Defense Physician Scientist Training Award. J.C.L. is a Camille Dreyfus Teacher-Scholar. We acknowledge the Arthur and Linda Gelb Center for Translational Research for the acquisition and annotation of clinical samples and A. Abbott and A. Van Den Abbeele from the Dana-Farber Cancer Institute (DFCI) Department of Imaging for positron-emission tomography (PET) images. We also acknowledge P.K. Brastianos (Department of Medical Oncology, DFCI) and I. Dunn (Department of Neurosurgery, Brigham and Women's Hospital) for contributing samples for CTC analysis, D. Peck for help with technology development, O. Voznesensky and S. Balk for purification of DNA from the metastatic tumor for sequencing, C. Whittaker and S.S. Levine for advice on sequencing and analysis and the Broad Genomics Platform for the development of new sequencing approaches used here. This work was also supported in part by the Koch Institute Support (core) grant P30-CA14051 from the National Cancer Institute, and we thank the Koch Institute Swanson Biotechnology Center for technical support, specifically the BioMicroCenter. This work was also supported in part by Janssen Pharmaceuticals, Inc. and the Klarman Family Foundation. We would like to thank Illumina for providing the MagSweeper. The authors dedicate this paper to the memory of Officer Sean Collier, for his caring service to the MIT community and for his sacrifice.

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Author notes

1. Jens G Lohr, Viktor A Adalsteinsson and Kristian Cibulskis: These authors contributed equally to this work.

Authors and Affiliations

1. The Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
   Jens G Lohr, Viktor A Adalsteinsson, Kristian Cibulskis, Atish D Choudhury, Mara Rosenberg, Peter Cruz-Gordillo, Joshua M Francis, Cheng-Zhong Zhang, Rahul Satija, John J Trombetta, Diana Lu, Sora Kim, Brendan Blumenstiel, Carrie Sougnez, Bang Wong, Daniel Auclair, Eliezer M Van Allen, Massimo Loda, Aviv Regev, Matthew Meyerson, William C Hahn, Todd R Golub, Gad Getz, Jesse S Boehm & J Christopher Love
2. Dana-Farber Cancer Institute, Boston, Massachusetts, USA
   Jens G Lohr, Atish D Choudhury, Joshua M Francis, Cheng-Zhong Zhang, Eliezer M Van Allen, Mari Nakabayashi, Rosina T Lis, Gwo-Shu M Lee, Tiantian Li, Matthew S Chabot, Mary-Ellen Taplin, Thomas E Clancy, Massimo Loda, Matthew Meyerson, William C Hahn, Philip W Kantoff & Todd R Golub
3. Harvard Medical School, Boston, Massachusetts, USA
   Jens G Lohr, Atish D Choudhury, Eliezer M Van Allen, Mari Nakabayashi, Mary-Ellen Taplin, Thomas E Clancy, Massimo Loda, Matthew Meyerson, William C Hahn, Philip W Kantoff & Todd R Golub
4. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
   Viktor A Adalsteinsson, Naren Tallapragada, Narmin Tahirova & J Christopher Love
5. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA
   Alex K Shalek
6. Brigham and Women's Hospital, Boston, Massachusetts, USA
   Alarice Lowe, Thomas E Clancy, Massimo Loda & William C Hahn
7. Massachusetts General Hospital, Boston, Massachusetts, USA
   Amy Ly & Gad Getz
8. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
   Aviv Regev
9. Howard Hughes Medical Institute, Chevy Chase, Maryland, USA
   Aviv Regev & Todd R Golub
10. Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA
    J Christopher Love

Authors

1. Jens G Lohr
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2. Viktor A Adalsteinsson
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3. Kristian Cibulskis
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4. Atish D Choudhury
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5. Mara Rosenberg
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6. Peter Cruz-Gordillo
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7. Joshua M Francis
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8. Cheng-Zhong Zhang
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9. Alex K Shalek
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10. Rahul Satija
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11. John J Trombetta
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12. Diana Lu
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13. Naren Tallapragada
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14. Narmin Tahirova
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15. Sora Kim
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16. Brendan Blumenstiel
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17. Carrie Sougnez
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18. Alarice Lowe
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19. Bang Wong
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20. Daniel Auclair
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21. Eliezer M Van Allen
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22. Mari Nakabayashi
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23. Rosina T Lis
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24. Gwo-Shu M Lee
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25. Tiantian Li
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26. Matthew S Chabot
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27. Amy Ly
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28. Mary-Ellen Taplin
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29. Thomas E Clancy
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30. Massimo Loda
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31. Aviv Regev
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32. Matthew Meyerson
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33. William C Hahn
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34. Philip W Kantoff
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35. Todd R Golub
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36. Gad Getz
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37. Jesse S Boehm
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38. J Christopher Love
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Contributions

J.G.L. and V.A.A. designed and performed experiments, analyzed data and wrote the manuscript. K.C. and M.R. developed computational methods, analyzed data and wrote the manuscript. A.D.C. provided clinical samples and patient data and analyzed clinical data. P.C.-G., N. Tahirova and S.K. performed experiments for isolating CTCs. J.M.F. developed single-cell sequencing methods and designed experiments. C.-Z.Z. analyzed data and applied the autocorrelation methods. A.K.S., R.S., J.J.T. and D.L. performed single-cell RNA sequencing and data analysis. N. Tallapragada developed code for determining CTCs to recover from nanowells. B.B. performed early technology development. C.S. and D.A. performed sample and data management and gave conceptual advice. A. Lowe and A. Ly performed experiments comparing our process to the Veridex CellSearch System. E.M.V.A. analyzed sequencing data. M.N., G.-S.M.L., T.L. and M.S.C. coordinated and acquired clinical samples. R.T.L. reviewed pathology slides and guided selection of clinical samples. B.W. performed data visualization. T.E.C. provided samples and validated methods for isolating CTCs. M.-E.T., M.L., A.R., M.M., W.C.H. and P.W.K. supervised experiments and sample and data collection and edited the manuscript. T.R.G., G.G., J.S.B. and J.C.L. designed the experimental strategy, supervised the analysis and wrote the manuscript. All authors discussed the results and implications and reviewed the manuscript.

Corresponding authors

Correspondence toGad Getz, Jesse S Boehm or J Christopher Love.

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Competing interests

J.C.L. is a founder and shareholder of Enumeral Biomedical Corp., holding a license for a patent on the specific design of the nanowells used in this study.

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Lohr, J., Adalsteinsson, V., Cibulskis, K. et al. Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer.Nat Biotechnol 32, 479–484 (2014). https://doi.org/10.1038/nbt.2892

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• Received: 25 October 2013
• Accepted: 30 March 2014
• Published: 20 April 2014
• Issue Date: May 2014
• DOI: https://doi.org/10.1038/nbt.2892