title: Presymptomatic Identification of Cancers in Pregnant Women During Noninvasive Prenatal Testing.
abstract: OBJECTIVE
  Noninvasive prenatal testing (NIPT) for fetal aneuploidy by scanning cell-free fetal DNA in maternal plasma is rapidly becoming a major prenatal genetic test. Similar to placental DNA, tumor DNA can be detected in the plasma, and analysis of cell-free tumor DNA can be used to characterize and monitor cancers. We show that plasma DNA profiling allows for presymptomatic detection of tumors in pregnant women undergoing routine NIPT.
  
  
  METHODS
  During NIPT in over 4000 prospective pregnancies by parallel sequencing of maternal plasma cell-free DNA, 3 aberrant genome representation (GR) profiles were observed that could not be attributed to the maternal or fetal genomic constitution. A maternal cancer was suspected, and those 3 patients were referred for whole-body diffusion-weighted magnetic resonance imaging, which uncovered an ovarian carcinoma, a follicular lymphoma, and a Hodgkin lymphoma, each confirmed by subsequent pathologic and genetic investigations. The copy number variations in the subsequent tumor biopsies were concordant with the NIPT plasma GR profiles.
  
  
  CONCLUSIONS
  We show that maternal plasma cell-free DNA sequencing for noninvasive prenatal testing also may enable accurate presymptomatic detection of maternal tumors and treatment during pregnancy.
authors.affiliation: Department of Obstetrics and Gynecology, Gynecological Oncology, Katholieke Universiteit (KU) Leuven-University of Leuven, University Hospitals, Leuven, Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Amant
authors.affiliation: Department of Obstetrics and Gynecology, Gynecological Oncology, Katholieke Universiteit (KU) Leuven-University of Leuven, University Hospitals, Leuven, Belgium.
authors.forename: Magali
authors.initials: M
authors.lastname: Verheecke
authors.affiliation: Center for Human Genetics, KU Leuven-University of Leuven, University Hospitals Leuven, Belgium.
authors.forename: Iwona
authors.initials: I
authors.lastname: Wlodarska
authors.affiliation: Center for Human Genetics, KU Leuven-University of Leuven, University Hospitals Leuven, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Dehaspe
authors.affiliation: Center for Human Genetics, KU Leuven-University of Leuven, University Hospitals Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Brady
authors.affiliation: Center for Human Genetics, KU Leuven-University of Leuven, University Hospitals Leuven, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Brison
authors.affiliation: Center for Human Genetics, KU Leuven-University of Leuven, University Hospitals Leuven, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: Van Den Bogaert
authors.affiliation: Department of Hematology, KU Leuven-University of Leuven, University Hospitals, Leuven, Belgium.
authors.forename: Daan
authors.initials: D
authors.lastname: Dierickx
authors.affiliation: Department of Radiology, KU Leuven-University of Leuven, Leuven, Flanders, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Vandecaveye
authors.affiliation: Department of Pathology, Translational Cell and Tissue Research, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tousseyn
authors.affiliation: Department of Pathology, Translational Cell and Tissue Research, KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moerman
authors.affiliation: Center for Human Genetics, KU Leuven-University of Leuven, University Hospitals Leuven, Belgium.
authors.forename: Adriaan
authors.initials: A
authors.lastname: Vanderstichele
authors.affiliation: Center for Human Genetics, KU Leuven-University of Leuven, University Hospitals Leuven, Belgium.
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.affiliation: Center for Human Genetics, KU Leuven-University of Leuven, University Hospitals Leuven, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Neven
authors.affiliation: Department of Obstetrics and Gynecology, Gynecologic Oncology, University Hospital, Leuven-General Hospital, Sint-Maarten Duffel, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Berteloot
authors.affiliation: Department of Obstetrics and Gynecology, General Hospital H. Hart, Leuven, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Putseys
authors.affiliation: Department of Obstetrics and Gynecology, General Hospital Delta, Roeselare, Belgium.
authors.forename: Lode
authors.initials: L
authors.lastname: Danneels
authors.affiliation: Center for Human Genetics, KU Leuven-University of Leuven, University Hospitals Leuven, Belgium3Department of Hematology, KU Leuven-University of Leuven, University Hospitals, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenberghe
authors.affiliation: Center for Human Genetics, KU Leuven-University of Leuven, University Hospitals Leuven, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Legius
authors.affiliation: Center for Human Genetics, KU Leuven-University of Leuven, University Hospitals Leuven, Belgium.
authors.forename: Joris Robert
authors.initials: JR
authors.lastname: Vermeesch
mesh_terms: D058070:Asymptomatic Diseases; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D001706:Biopsy; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006689:Hodgkin Disease / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008224:Lymphoma, Follicular / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D010641:Phenotype; D011237:Predictive Value of Tests; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D011296:Prenatal Diagnosis / Q000379:methods*; D011379:Prognosis; D051598:Whole Body Imaging
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm