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

William M. Strauss, Chris Carter, Jill Simmons, Erich Klem, Nathan Goodman, Behrad Vahidi, Juan Romero, Michael Masterman-Smith, Ruth O'Regan, Keerthi Gogineni, Lee Schwartzberg, Laura K. Austin, Paul W. Dempsey*, Massimo Cristofanilli

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)26724-26738
Number of pages15
JournalOncotarget
Volume7
Issue number18
DOIs
StatePublished - May 1 2016

Keywords

  • CTC
  • CfDNA
  • Liquid biopsy
  • Metastatic breast cancer
  • Next generation sequence

ASJC Scopus subject areas

  • Oncology

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