title: Quantification of Somatic Chromosomal Rearrangements in Circulating Cell-Free DNA from Ovarian Cancers.
abstract: Recently, the use of a liquid biopsy has shown promise in monitoring tumor burden. While point mutations have been extensively studied, chromosomal rearrangements have demonstrated greater tumor specificity. Such rearrangements can be identified in the tumor and subsequently detected in the plasma of patients using quantitative PCR (qPCR). In this study we used a whole-genome mate-pair protocol to characterize a landscape of genomic rearrangements in the primary tumors of ten ovarian cancer patients. Individualized tumor-specific primer panels of aberrant chromosomal junctions were identified for each case and detected by qPCR within the cell-free DNA. Selected chromosomal junctions were detected in pre-surgically drawn blood in eight of the ten patients. Of these eight, three demonstrated the continued presence of circulating tumor DNA (ctDNA) post-surgery, consistent with their documented presence of disease, and in five ctDNA was undetectable in the post-surgical blood collection, consistent with their lack of detectable disease. The ctDNA fraction was calculated using a novel algorithm designed for the unique challenges of quantifying ctDNA using qPCR to allow observations of real-time tumor dynamics. In summary, a panel of individualized junctions derived from tumor DNA could be an effective way to monitor cancer patients for relapse and therapeutic efficacy using cfDNA.
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Faye R
authors.initials: FR
authors.lastname: Harris
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Kovtun
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: James
authors.initials: J
authors.lastname: Smadbeck
authors.affiliation: Gynecology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Multinu
authors.affiliation: Medical Oncology, Mayo Clinic, Rochester, MN 55905 USA.
authors.forename: Aminah
authors.initials: A
authors.lastname: Jatoi
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Farhad
authors.initials: F
authors.lastname: Kosari
authors.affiliation: Medical Oncology, Mayo Clinic, Rochester, MN 55905 USA.
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Kalli
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Murphy
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Halling
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Johnson
authors.affiliation: Medical Oncology, Mayo Clinic, Rochester, MN 55905 USA.
authors.forename: Minetta C
authors.initials: MC
authors.lastname: Liu
authors.affiliation: Gynecology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mariani
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: George
authors.initials: G
authors.lastname: Vasmatzis
mesh_terms: D000073888:Cell-Free Nucleic Acids / Q000032:analysis* / Q000097:blood / Q000235:genetics; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000032:analysis* / Q000097:blood / Q000235:genetics; D005260:Female; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics; D017063:Outcome Assessment, Health Care / Q000379:methods; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics* / Q000601:surgery; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D047368:Tumor Burden / Q000235:genetics
chemical_list: D000073888:Cell-Free Nucleic Acids; D004273:DNA, Neoplasm