title: Analysis of tumor template from multiple compartments in a blood sample provides complementary access to peripheral tumor biomarkers.
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.
authors.affiliation: Cynvenio Biosystems, Westlake Village, CA, 91361, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Strauss
authors.affiliation: Cynvenio Biosystems, Westlake Village, CA, 91361, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Carter
authors.affiliation: Cynvenio Biosystems, Westlake Village, CA, 91361, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Simmons
authors.affiliation: Cynvenio Biosystems, Westlake Village, CA, 91361, USA.
authors.forename: Erich
authors.initials: E
authors.lastname: Klem
authors.affiliation: Independent, Seattle, WA, 98109, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Goodman
authors.affiliation: Cynvenio Biosystems, Westlake Village, CA, 91361, USA.
authors.forename: Behrad
authors.initials: B
authors.lastname: Vahidi
authors.affiliation: Cynvenio Biosystems, Westlake Village, CA, 91361, USA.|Current address: Xencor, Inc, Monrovia, CA, 91016, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Romero
authors.affiliation: Cynvenio Biosystems, Westlake Village, CA, 91361, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Masterman-Smith
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Center, Emory University, Atlanta, GA, 30322, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: O'Regan
authors.affiliation: Division of Hematology/Oncology, University of Wisconsin, Madison, WI, 53792, USA.
authors.forename: Keerthi
authors.initials: K
authors.lastname: Gogineni
authors.affiliation: The West Clinic, Germantown, TN, 38138, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Schwartzberg
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA,19107, USA.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Austin
authors.affiliation: Cynvenio Biosystems, Westlake Village, CA, 91361, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Dempsey
authors.affiliation: Lurie Cancer Center, Northwestern University, Chicago, IL, 60611, USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics*; D000074141:Circulating Tumor DNA / Q000097:blood*; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating
chemical_list: D014408:Biomarkers, Tumor; D000074141:Circulating Tumor DNA
keywords: CTC; cfDNA; liquid biopsy; metastatic breast cancer; next generation sequence