Molecular inversion probe array for the genetic evaluation of stillbirth using formalin-fixed, paraffin-embedded tissue

Leslie R. Rowe, Harshwardhan Thaker, John M. Opitz, Joshua D. Schiffman, Zaid M. Haddadin, Lance K. Erickson, Sarah T. South

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Array comparative hybridization has been used successfully to identify genomic alterations in stillbirth material; however, high DNA quantity and quality requirements may limit its utility in some fetal samples. Molecular inversion probe (MIP) array analysis of FFPE stillbirth autopsy samples circumvents the challenges associated with karyotype and short-term fetal cell culture, requires limited DNA input, and allows for retrospective evaluation of fetal loss. We performed MIP analysis on archival FFPE autopsy tissue to identify underlying genetic abnormalities not previously detected using traditional cytogenetic methods. Archival FFPE stillbirth cases (≥20 weeks gestation) were identified with the following characteristics: i) the phenotype suggested underlying genomic alterations; ii) the karyotype was either normal or not available and there were no other known genetic abnormalities; or iii) previous microarray testing was not performed. Genomic DNA (75 ng) was processed onto a 330,000-feature MIP array. Twenty-seven of 29 (93.1%) FFPE samples had passing MIP quality control scores. Abnormalities were seen in 3 of 27 (11%) archival samples (deletion of 17q12, trisomy 18, and a case of 4qter duplication and 13qter deletion arising from an unbalanced 4q;13q translocation), which, if identified at the time of autopsy, may have changed the course of medical management. This study highlights the benefits of using MIP array analysis for identification of genomic alterations in FFPE stillbirth autopsy tissue.

Original languageEnglish (US)
Pages (from-to)466-472
Number of pages7
JournalJournal of Molecular Diagnostics
Volume15
Issue number4
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

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Molecular Probes
Stillbirth
Paraffin
Formaldehyde
Autopsy
Karyotype
DNA
Cytogenetics
Quality Control
Cell Culture Techniques
Phenotype
Pregnancy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine

Cite this

Molecular inversion probe array for the genetic evaluation of stillbirth using formalin-fixed, paraffin-embedded tissue. / Rowe, Leslie R.; Thaker, Harshwardhan; Opitz, John M.; Schiffman, Joshua D.; Haddadin, Zaid M.; Erickson, Lance K.; South, Sarah T.

In: Journal of Molecular Diagnostics, Vol. 15, No. 4, 01.07.2013, p. 466-472.

Research output: Contribution to journalArticle

Rowe, Leslie R. ; Thaker, Harshwardhan ; Opitz, John M. ; Schiffman, Joshua D. ; Haddadin, Zaid M. ; Erickson, Lance K. ; South, Sarah T. / Molecular inversion probe array for the genetic evaluation of stillbirth using formalin-fixed, paraffin-embedded tissue. In: Journal of Molecular Diagnostics. 2013 ; Vol. 15, No. 4. pp. 466-472.
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