Analysis of tumor template from multiple compartments in a blood sample provides complementary access to peripheral tumor biomarkers
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William M. Strauss1, Chris Carter1, Jill Simmons1, Erich Klem1, Nathan Goodman2, Behrad Vahidi1, Juan Romero1,8, Michael Masterman-Smith1, Ruth O’Regan3, Keerthi Gogineni4, Lee Schwartzberg5, Laura K. Austin6, Paul W. Dempsey1, Massimo Cristofanilli7
1Cynvenio Biosystems, Westlake Village, CA, 91361, USA
2Independent, Seattle, WA, 98109, USA
3Department of Hematology and Medical Oncology, Winship Cancer Center, Emory University, Atlanta, GA, 30322, USA
4Division of Hematology/Oncology, University of Wisconsin, Madison, WI, 53792, USA
5The West Clinic, Germantown, TN, 38138, USA
6Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA,19107, USA
7Lurie Cancer Center, Northwestern University, Chicago, IL, 60611, USA
8Current Address: Xencor, Inc, Monrovia, CA 91016, USA
Paul W. Dempsey, e-mail: firstname.lastname@example.org
Keywords: liquid biopsy, CTC, cfDNA, metastatic breast cancer, next generation sequence
Received: December 23, 2015 Accepted: March 14, 2016 Published: March 30, 2016
Targeted cancer therapeutics are promised to have a major impact on cancer treatment and survival. Successful application of these novel treatments requires a molecular definition of a patient’s disease typically achieved through the use of tissue biopsies. Alternatively, allowing longitudinal monitoring, biomarkers derived from blood, isolated either from circulating tumor cell derived DNA (ctcDNA) or circulating cell-free tumor DNA (ccfDNA) may be evaluated. In order to use blood derived templates for mutational profiling in clinical decisions, it is essential to understand the different template qualities and how they compare to biopsy derived template DNA as both blood-based templates are rare and distinct from the gold-standard. Using a next generation re-sequencing strategy, concordance of the mutational spectrum was evaluated in 32 patient-matched ctcDNA and ccfDNA templates with comparison to tissue biopsy derived DNA template. Different CTC antibody capture systems for DNA isolation from patient blood samples were also compared. Significant overlap was observed between ctcDNA, ccfDNA and tissue derived templates. Interestingly, if the results of ctcDNA and ccfDNA template sequencing were combined, productive samples showed similar detection frequency (56% vs 58%), were temporally flexible, and were complementary both to each other and the gold standard. These observations justify the use of a multiple template approach to the liquid biopsy, where germline, ctcDNA, and ccfDNA templates are employed for clinical diagnostic purposes and open a path to comprehensive blood derived biomarker access.
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