Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer

Jeanne Tie; Yuxuan Wang; Cristian Tomasetti; Lu Li; Simeon Springer; Isaac Kinde; Natalie Silliman; Mark Tacey; Hui-Li Wong; Michael Christie; Suzanne Kosmider; Iain Skinner; Rachel Wong; Malcolm Steel; Ben Tran; Jayesh Desai; Ian Jones; Andrew Haydon; Theresa Hayes; Tim J. Price; Robert L. Strausberg; Luis A. Diaz; Nickolas Papadopoulos; Kenneth W. Kinzler; Bert Vogelstein; Peter Gibbs

doi:10.1126/scitranslmed.aaf6219

Research ArticleCancer

Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer

Jeanne Tie¹,²,³,⁴,*,†,
Yuxuan Wang⁵,†,
Cristian Tomasetti⁶,⁷,
Lu Li⁶,
Simeon Springer⁵,
Isaac Kinde⁸,
Natalie Silliman⁵,
Mark Tacey⁹,
Hui-Li Wong¹,³,⁴,
Michael Christie¹,³,¹⁰,
Suzanne Kosmider²,
Iain Skinner²,
Rachel Wong¹,¹¹,¹²,
Malcolm Steel¹¹,
Ben Tran¹,²,³,⁴,
Jayesh Desai¹,³,⁴,
Ian Jones⁴,¹³,
Andrew Haydon¹⁴,
Theresa Hayes¹⁵,
Tim J. Price¹⁶,
Robert L. Strausberg¹⁷,
Luis A. Diaz Jr.⁵,
Nickolas Papadopoulos⁵,
Kenneth W. Kinzler⁵,
Bert Vogelstein⁵,*,† and
Peter Gibbs¹,²,³,⁴,¹⁷,*,†

¹Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
²Department of Medical Oncology, Western Health, St Albans, Victoria 3021, Australia.
³Department of Medical Oncology,
⁴Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia.
⁵Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
⁶Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁷Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
⁸PapGene Inc., Baltimore, MD 21211, USA.
⁹Melbourne EpiCentre, Department of Medicine, University of Melbourne, Parkville, Victoria 3010, Australia.
¹⁰Department of Pathology, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
¹¹Department of Medical Oncology, Eastern Health, Box Hill, Victoria 3128, Australia.
¹²Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria 3800, Australia.
¹³Department of Surgery, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
¹⁴Department of Medical Oncology, Alfred Hospital, Melbourne, Victoria 3004, Australia.
¹⁵Department of Medical Oncology, Warrnambool Hospital, Warrnambool, Victoria 3280, Australia.
¹⁶Department of Medical Oncology, Queen Elizabeth Hospital and University of Adelaide, Adelaide, South Australia 3174, Australia.
¹⁷Ludwig Institute for Cancer Research, New York, NY 10017, USA.

↵*Corresponding author. Email: jeanne.tie{at}mh.org.au (J.T.); vogelbe{at}jhmi.edu (B.V.); peter.gibbs{at}mh.org.au (P.G.)

↵† These authors contributed equally to this work.

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Science Translational Medicine 06 Jul 2016:
Vol. 8, Issue 346, pp. 346ra92
DOI: 10.1126/scitranslmed.aaf6219

Jeanne Tie

1Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

2Department of Medical Oncology, Western Health, St Albans, Victoria 3021, Australia.

3Department of Medical Oncology,

4Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia.

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For correspondence: jeanne.tie@mh.org.au vogelbe@jhmi.edu peter.gibbs@mh.org.au

Yuxuan Wang

5Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.

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Cristian Tomasetti

6Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

7Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.

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Lu Li

6Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

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Simeon Springer

5Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.

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Isaac Kinde

8PapGene Inc., Baltimore, MD 21211, USA.

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Natalie Silliman

5Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.

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Mark Tacey

9Melbourne EpiCentre, Department of Medicine, University of Melbourne, Parkville, Victoria 3010, Australia.

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Hui-Li Wong

1Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

3Department of Medical Oncology,

4Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia.

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Michael Christie

1Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

3Department of Medical Oncology,

10Department of Pathology, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.

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Suzanne Kosmider

2Department of Medical Oncology, Western Health, St Albans, Victoria 3021, Australia.

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Iain Skinner

2Department of Medical Oncology, Western Health, St Albans, Victoria 3021, Australia.

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Rachel Wong

1Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

11Department of Medical Oncology, Eastern Health, Box Hill, Victoria 3128, Australia.

12Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria 3800, Australia.

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Malcolm Steel

11Department of Medical Oncology, Eastern Health, Box Hill, Victoria 3128, Australia.

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Ben Tran

1Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

2Department of Medical Oncology, Western Health, St Albans, Victoria 3021, Australia.

3Department of Medical Oncology,

4Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia.

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Jayesh Desai

1Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

3Department of Medical Oncology,

4Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia.

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Ian Jones

4Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia.

13Department of Surgery, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.

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Andrew Haydon

14Department of Medical Oncology, Alfred Hospital, Melbourne, Victoria 3004, Australia.

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Theresa Hayes

15Department of Medical Oncology, Warrnambool Hospital, Warrnambool, Victoria 3280, Australia.

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Tim J. Price

16Department of Medical Oncology, Queen Elizabeth Hospital and University of Adelaide, Adelaide, South Australia 3174, Australia.

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Robert L. Strausberg

17Ludwig Institute for Cancer Research, New York, NY 10017, USA.

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Luis A. Diaz Jr.

5Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.

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Nickolas Papadopoulos

5Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.

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Kenneth W. Kinzler

5Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.

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Bert Vogelstein

5Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.

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For correspondence: jeanne.tie@mh.org.au vogelbe@jhmi.edu peter.gibbs@mh.org.au

Peter Gibbs

1Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

2Department of Medical Oncology, Western Health, St Albans, Victoria 3021, Australia.

3Department of Medical Oncology,

4Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia.

17Ludwig Institute for Cancer Research, New York, NY 10017, USA.

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For correspondence: jeanne.tie@mh.org.au vogelbe@jhmi.edu peter.gibbs@mh.org.au

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Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer

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