Abstract
BackgroundThe 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).ResultsFresh 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.ConclusionOMA 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.
Highlights
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
During 2018–2020, 94 cases of products of conception (POC)-normal karyotype (NK), 38 cases of POC-culture failure (CF), and 35 cases of POC-formalin-fixed paraffin-embedded (FFPE) analyzed by OMA were retrieved from the laboratory’s information system [12]
Of the ten abnormal cases in POC-CF, aneuploidies, triploidies and pathogenic copy number variants (pCNV) accounted for 50% (5/10), 40% (4/10) and 10% (1/10), respectively
Summary
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). Karyotyping analysis on culture cells from fresh POC specimens detected numerical aneuploidies and polyploidies as well as structural chromosomal abnormalities in approximately 50% of specimens; for the remaining 50% with a normal karyotype (NK), microarray analysis detected pathogenic copy number variants (pCNVs) and uniparental disomy in approximately 2–4% and 1–2% of specimens, respectively [2,3,4]. A salvage procedure using microarray analysis on POC-CF could detect cytogenomic abnormalities in 35% of cases and a strategy of initial karyotyping on culture success cases followed by microarray analysis on POC-NK and POC-CF cases has been implemented [3]
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