Sahoo Trilochan, Dzidic Natasa, Strecker Michelle N, Commander Sara, Travis Mary K, Doherty Charles, Tyson R Weslie, Mendoza Arturo E, Stephenson Mary, Dise Craig A, Benito Carlos W, Ziadie Mandolin S, Hovanes Karine
CombiMatrix Diagnostics, Irvine, California, USA.
Department of Pathology, SCL Health System, Denver, Colorado, USA.
Genet Med. 2017 Jan;19(1):83-89. doi: 10.1038/gim.2016.69. Epub 2016 Jun 23.
Chromosomal microarray analysis (CMA) is currently considered first-tier testing in pediatric care and prenatal diagnosis owing to its high diagnostic sensitivity for chromosomal imbalances. The aim of this study was to determine the efficacy and diagnostic power of CMA in both fresh and formalin-fixed paraffin-embedded (FFPE) samples of products of conception (POCs).
Over a 44-month period, 8,118 consecutive samples were received by our laboratory for CMA analysis. This included both fresh (76.4%) and FFPE samples (22.4%), most of which were ascertained for recurrent pregnancy loss and/or spontaneous abortion (83%). The majority of samples were evaluated by a whole-genome single-nucleotide polymorphism (SNP)-based array (81.6%); the remaining samples were evaluated by array-comparative genomic hybridization (CGH).
A successful result was obtained in 7,396 of 8,118 (91.1%), with 92.4% of fresh tissue samples and 86.4% of FFPE samples successfully analyzed. Clinically significant abnormalities were identified in 53.7% of specimens (3,975 of 7,396), 94% of which were considered causative.
Analysis of POC specimens by karyotyping fails in 20-40% of cases. SNP-based CMA is a robust platform, with successful results obtained in >90% of cases. SNP-based CMA can identify aneuploidy, polyploidy, whole-genome homozygosity, segmental genomic imbalances, and maternal cell contamination, thus maximizing sensitivity and decreasing false-negative results. Understanding the etiology of fetal loss enables clarification of recurrence risk and assists in determining appropriate management for future family planning.Genet Med 19 1, 83-89.
由于染色体微阵列分析（CMA）对染色体失衡具有较高的诊断敏感性，目前被认为是儿科护理和产前诊断的一线检测方法。本研究的目的是确定CMA在新鲜及福尔马林固定石蜡包埋（FFPE）的妊娠产物（POC）样本中的有效性和诊断能力。
在44个月的时间里，我们实验室共接收了8118份连续样本进行CMA分析。其中包括新鲜样本（76.4%）和FFPE样本（22.4%），大多数样本是因复发性流产和/或自然流产而送检（83%）。大多数样本通过基于全基因组单核苷酸多态性（SNP）的芯片进行评估（81.6%）；其余样本通过阵列比较基因组杂交（CGH）进行评估。
8118份样本中有7396份（91.1%）获得了成功结果，新鲜组织样本的成功分析率为92.4%，FFPE样本的成功分析率为86.4%。在53.7%的标本（7396份中的3975份）中发现了具有临床意义的异常，其中94%被认为是病因性的。
通过核型分析对POC标本进行分析时，20%-40%的病例会失败。基于SNP的CMA是一个强大的平台，90%以上的病例都能获得成功结果。基于SNP的CMA可以识别非整倍体、多倍体、全基因组纯合性、节段性基因组失衡和母体细胞污染，从而最大限度地提高敏感性并减少假阴性结果。了解胎儿丢失的病因有助于明确复发风险，并协助确定未来计划生育的适当管理措施。《遗传医学》19卷1期，83-89页。
