Detection of cytogenomic abnormalities by OncoScan microarray assay for products of conception from formalin-fixed paraffin-embedded and fresh fetal tissues

Jiadi Wen; Brittany Grommisch; Autumn DiAdamo; Hongyan Chai; Sok Meng Evelyn Ng; Pei Hui; Allen Bale; Winifred Mak; Guilin Wang; Peining Li

doi:10.1186/s13039-021-00542-5

Detection of cytogenomic abnormalities by OncoScan microarray assay for products of conception from formalin-fixed paraffin-embedded and fresh fetal tissues

Mol Cytogenet. 2021 Apr 2;14(1):21. doi: 10.1186/s13039-021-00542-5.

Authors

Affiliations

¹ Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
² Yale Center for Genome Analysis, Yale University School of Medicine, New Haven, CT, USA.
³ Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
⁴ Department of Women's Health, Dell Medical School, The University of Texas At Austin, Austin, TX, USA.
⁵ Yale Center for Genome Analysis, Yale University School of Medicine, New Haven, CT, USA. guilin.wang@yale.edu.
⁶ Department of Genetics, Yale University School of Medicine, New Haven, CT, USA. peining.li@yale.edu.

Abstract

Background: The OncoScan microarray assay (OMA) using highly multiplexed molecular inversion probes for single nucleotide polymorphism (SNP) loci enabled the detection of cytogenomic abnormalities of chromosomal imbalances and pathogenic copy number variants (pCNV). The small size of molecular inversion probes is optimal for SNP genotyping of fragmented DNA from fixed tissues. This retrospective study evaluated the clinical utility of OMA as a uniform platform to detect cytogenomic abnormalities for pregnancy loss from fresh and fixed tissues of products of conception (POC).

Results: Fresh specimens of POC were routinely subjected to cell culture and then analyzed by karyotyping. POC specimens with a normal karyotype (NK) or culture failure (CF) and from formalin-fixed paraffin-embedded (FFPE) tissues were subjected to DNA extraction for OMA. The abnormality detection rate (ADR) by OMA on 94 cases of POC-NK, 38 cases of POC-CF, and 35 cases of POC-FFPE tissues were 2% (2/94), 26% (10/38), and 57% (20/35), respectively. The detected cytogenomic abnormalities of aneuploidies, triploidies and pCNV accounted for 50%, 40% and 10% in POC-CF and 85%, 10% and 5% in POC-FFPE, respectively. False negative result from cultured maternal cells and maternal cell contamination were each detected in one case. OMA on two cases with unbalanced structural chromosome abnormalities further defined genomic imbalances and breakpoints.

Conclusion: OMA on POC-CF and POC-FFPE showed a high diagnostic yield of cytogenomic abnormalities. This approach circumvented the obstacles of CF from fresh specimens and fragmented DNA from fixed tissues and provided a reliable and effective platform for detecting cytogenomic abnormalities and monitoring true fetal result from maternal cell contamination.

Keywords: Aneuploidy; Formalin-fixed paraffin-embedded (FFPE) tissue; OncoScan microarray assay (OMA); Pathogenic copy number variant (pCNV); Polyploidy; Products of conception (POC).