title: Stillbirth: Genome-wide copy number variation profiling in archived placental umbilical cord samples with pathologic and clinical correlation.
abstract: BACKGROUND
  Stillbirth remains a devastating health issue with 26,000 stillbirths occurring annually in the United States. Formalin-fixed, paraffin-embedded (FFPE) umbilical cord samples are available for many stillbirths. Our aim was to validate the use of these samples in identifying genetic variations in stillbirth through microarray analysis.
  
  
  METHODS
  This is a retrospective case-control study from a single institution of stillbirths ≥ 23 weeks gestational age and control liveborn infants. Fetal genomic DNA was extracted from FFPE umbilical cord samples of stillborn and control placentas, and genotyping was performed using the Illumina HumanOmniExpresss-12v1 Beadchip. Array results were verified with qPCR.
  
  
  RESULTS
  31 case-specific CNVs (17 deletions and 14 amplifications) with an average size of 294 kb for amplifications and 74 kb for deletions were identified among 94 FFPE samples (86 cases; 8 controls). In total 38 (44%) of the stillbirth samples had a CNV detected. Validation of a subset of microarray findings with qPCR confirmed deletions on 1p (2 cases), 11q (4 cases) and amplifications on 18 (1 case). Placental underperfusion changes were seen in stillborns with deletions on 1p, a region containing complement regulatory genes which have been shown to play a role in preeclampsia.
  
  
  CONCLUSIONS
  This study validated the use of archived FFPE umbilical cord samples for genome-wide copy number profiling in stillbirths, and demonstrates specific CNV deletions and amplifications. Microarray analysis in an expanded cohort of stillbirth FFPE samples has the potential to identify biomarkers involved in stillbirth pathogenesis.
authors.affiliation: Northwestern University, Feinberg School of Medicine, Department of Pathology, USA. Electronic address: linda-ernst@northwestern.edu.
authors.forename: L M
authors.initials: LM
authors.lastname: Ernst
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago, Center for Autonomic Medicine in Pediatrics (CAMP) and Stanley Manne Children's Research Institute, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Rand
authors.affiliation: University of Chicago, Center for Research Informatics, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bao
authors.affiliation: University of Chicago, Center for Research Informatics, USA.
authors.forename: J
authors.initials: J
authors.lastname: Andrade
authors.affiliation: Northwestern University, Feinberg School of Medicine, Department of Pathology, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Linn
authors.affiliation: Northwestern University, Feinberg School of Medicine, Department of Pathology, USA.
authors.forename: L
authors.initials: L
authors.lastname: Minturn
authors.affiliation: University of Chicago, Center for Research Informatics, USA.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: University of Chicago, Center for Research Informatics, USA.
authors.forename: W
authors.initials: W
authors.lastname: Kang
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago, Center for Autonomic Medicine in Pediatrics (CAMP) and Stanley Manne Children's Research Institute, USA; Northwestern University, Feinberg School of Medicine, Department of Pediatrics, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Weese-Mayer
mesh_terms: D016022:Case-Control Studies; D002869:Chromosome Aberrations; D056915:DNA Copy Number Variations; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D008297:Male; D010920:Placenta / Q000473:pathology*; D010927:Placental Insufficiency / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D012189:Retrospective Studies; D050497:Stillbirth / Q000235:genetics*; D014470:Umbilical Cord / Q000473:pathology*
keywords: Fetal autopsy; Formalin-fixed paraffin embedded tissue; Placental pathology; Single nucleotide polymorphism (SNP) microarray