Analysis of tumor template from multiple compartments in a blood sample provides complementary access to peripheral tumor biomarkers

• Type of Material: Article
• Authors: William M. Strauss, Cynvenio Biosystems; Chris Carter, Cynvenio Biosystems; Jill Simmons, Cynvenio Biosystems; Erich Klem, Cynvenio Biosystems; Nathan Goodman, Independent, Seattle; Behrad Vahidi, Cynvenio Biosystems; Juan Romero, Cynvenio Biosystems; Michael Masterman-Smith, Cynvenio Biosystems; Ruth O'Regan, Emory University; Keerthi Gogineni, Emory University; Lee Schwartzberg, West Clinic Germantown; Laura K. Austin, Thomas Jefferson University; Paul W. Dempsey, Cynvenio Biosystems; Massimo Cristofanilli, Northwestern University
• Language: English
• Date: 2016-05-03
• Publisher: Impact Journals LLC.
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Impact Journals LLC.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.18632/oncotarget.8494
• Title of Journal or Parent Work: Oncotarget
• Volume: 7
• Issue: 18
• Start Page: 26724
• End Page: 26738
• Grant/Funding Information: The clinical study was supported by the Small Business Innovation Research Program (SBIR), RFP No. N44C031014-51 SBIR Phase II Topic 293: Development of Devices for Point of Care Analysis of Circulating Tumor Cells. Contract No. HHSN261201300073C.
• Keywords: Science & Technology; Chemotherapy; Metastatic breast cancer; metastatic breast cancer; Plasma; Gene amplification; Heterogeneity; Cell Biology; cfDNA; Free DNA; CTC; next generation sequence; Resistance; Abiraterone; Circulating epithelial cells; Life Sciences & Biomedicine; Oncology; Mutations; liquid biopsy
• Research Categories: Health Sciences, Oncology; Biology, Genetics; Biology, Cell

Abstract

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.