1. Detection of cytogenomic abnormalities by OncoScan microarray assay for products of conception from formalin-fixed paraffin-embedded and fresh fetal tissues
- Author
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Pei Hui, Guilin Wang, Jiadi Wen, Brittany Grommisch, Allen E. Bale, Peining Li, Sok Meng Evelyn Ng, Hongyan Chai, Autumn DiAdamo, and Winifred Mak
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Pathogenic copy number variant (pCNV) ,lcsh:QH426-470 ,Aneuploidy ,Formalin-fixed paraffin-embedded (FFPE) tissue ,030105 genetics & heredity ,Biology ,Biochemistry ,Polyploidy ,03 medical and health sciences ,Genetics ,medicine ,OncoScan microarray assay (OMA) ,Copy-number variation ,Molecular Biology ,Genetics (clinical) ,Products of conception (POC) ,Research ,Biochemistry (medical) ,Cytogenetics ,Chromosome ,Karyotype ,medicine.disease ,Molecular biology ,DNA extraction ,SNP genotyping ,lcsh:Genetics ,030104 developmental biology ,Products of conception ,Molecular Medicine - 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.
- Published
- 2021