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Clinical Studies

Genomic Alterations in Circulating Tumor DNA from Diverse Cancer Patients Identified by Next-Generation Sequencing

Maria Schwaederle, Ranajoy Chattopadhyay, Shumei Kato, Paul T. Fanta, Kimberly C. Banks, In Sil Choi, David E. Piccioni, Sadakatsu Ikeda, AmirAli Talasaz, Richard B. Lanman, Lyudmila Bazhenova and Razelle Kurzrock
Maria Schwaederle
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, California.
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Ranajoy Chattopadhyay
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, California.
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  • For correspondence: rchattopadhyay@ucsd.edu
Shumei Kato
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, California.
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Paul T. Fanta
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, California.
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Kimberly C. Banks
Guardant Health, Inc., Redwood City, California.
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In Sil Choi
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, California.
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David E. Piccioni
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, California.
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Sadakatsu Ikeda
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, California.
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AmirAli Talasaz
Guardant Health, Inc., Redwood City, California.
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Richard B. Lanman
Guardant Health, Inc., Redwood City, California.
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Lyudmila Bazhenova
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, California.
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Razelle Kurzrock
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, California.
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DOI: 10.1158/0008-5472.CAN-17-0885 Published October 2017
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Abstract

Noninvasive genomic profiling of tumors may be possible with next-generation sequencing (NGS) of blood-derived circulating tumor DNA (ctDNA), but proof of concept in a large cohort of patients with diverse cancers has yet to be reported. Here we report the results of an analysis of plasma-derived ctDNA from 670 patients with diverse cancers. The tumors represented in the patient cohort were mainly gastrointestinal (31.8%), brain (22.7%), or lung (20.7%). ctDNA obtained from most patients [N = 423 (63%)] displayed at least one alteration. The most frequent alterations seen, as characterized mutations or variants of unknown significance, occurred in TP53 (32.5% of patients), EGFR (13%), KRAS (12.5%), and PIK3CA (9.1%); for characterized alterations, 30.7% (TP53), 7.6% (EGFR), 12.2% (KRAS), and 7.7% (PIK3CA). We found that 32% of brain tumors had at least one ctDNA alteration. Head and neck tumors were independently associated with a higher number of alterations in a multivariable analysis (P = 0.019). Notably, 320/670 (48%) of patients displayed potentially actionable alterations, with 241 patients possible candidates for on-label or off-label treatment with an FDA-approved drug. Several illustrations of the clinical utility of the information obtained for improving treatment of specific patients is provided. Our findings demonstrate the feasibility and impact of genomic profiling of tumors by ctDNA NGS, greatly encouraging broader investigations of the application of this technology for precision medicine in cancer management. Cancer Res; 77(19); 5419–27. ©2017 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received April 12, 2017.
  • Revision received June 23, 2017.
  • Accepted August 1, 2017.
  • ©2017 American Association for Cancer Research.
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Cancer Research: 77 (19)
October 2017
Volume 77, Issue 19
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Genomic Alterations in Circulating Tumor DNA from Diverse Cancer Patients Identified by Next-Generation Sequencing
Maria Schwaederle, Ranajoy Chattopadhyay, Shumei Kato, Paul T. Fanta, Kimberly C. Banks, In Sil Choi, David E. Piccioni, Sadakatsu Ikeda, AmirAli Talasaz, Richard B. Lanman, Lyudmila Bazhenova and Razelle Kurzrock
Cancer Res October 1 2017 (77) (19) 5419-5427; DOI: 10.1158/0008-5472.CAN-17-0885

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Genomic Alterations in Circulating Tumor DNA from Diverse Cancer Patients Identified by Next-Generation Sequencing
Maria Schwaederle, Ranajoy Chattopadhyay, Shumei Kato, Paul T. Fanta, Kimberly C. Banks, In Sil Choi, David E. Piccioni, Sadakatsu Ikeda, AmirAli Talasaz, Richard B. Lanman, Lyudmila Bazhenova and Razelle Kurzrock
Cancer Res October 1 2017 (77) (19) 5419-5427; DOI: 10.1158/0008-5472.CAN-17-0885
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Cancer Research Online ISSN: 1538-7445
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