Assessment and Clinical Utility of a Non-Next-Generation Sequencing-Based Non-Invasive Prenatal Testing Technology

Current Issues in Molecular Biology

Bao Ping Choo¹  Lee Yin Chan¹  Yong Wee Wong¹  Liza Oraha²  Uzay Gormus²  Suresh Shenoy³  Ephrem Chin³  Alka Chaubey³  Madhuri Hegde³  Lawrence Prensky⁴  Anna Gousseva⁵  Fredrik Persson⁵ 

[1] DNA Laboratories Sdn. Bhd, PerkinElmer Genomics Malaysia, Bangi 43650, Selangor, Malaysia;PerkinElmer Genomics Sweden, 191 38 Sollentuna, Sweden;PerkinElmer Genomics, Pittsburgh, PA 15275, USA;PerkinElmer Inc., Waltham, MA 02451, USA;Vanadis Diagnostics, PerkinElmer Inc., 191 38 Sollentuna, Sweden;

关键词: cell-free DNA;    noninvasive prenatal screening;    noninvasive prenatal testing;    NIPT;    NIPS;    validation study;   

DOI  :  10.3390/cimb43020068

来源: DOAJ

【 摘 要 】

Background: Rolling-circle replication (RCR) is a novel technology that has not been applied to cell-free DNA (cfDNA) testing until recently. Given the cost and simplicity advantages of this technology compared to other platforms currently used in cfDNA analysis, an assessment of RCR in clinical laboratories was performed. Here, we present the first validation study from clinical laboratories utilizing RCR technology. Methods: 831 samples from spontaneously pregnant women carrying a singleton fetus, and 25 synthetic samples, were analyzed for the fetal risk of trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13), by three laboratories on three continents. All the screen-positive pregnancies were provided post-test genetic counseling and confirmatory diagnostic invasive testing (e.g., amniocentesis). The screen-negative pregnancies were routinely evaluated at birth for fetal aneuploidies, using newborn examinations, and any suspected aneuploidies would have been offered diagnostic testing or confirmed with karyotyping. Results: The study found rolling-circle replication to be a highly viable technology for the clinical assessment of fetal aneuploidies, with 100% sensitivity for T21 (95% CI: 82.35–100.00%); 100.00% sensitivity for T18 (71.51–100.00%); and 100.00% sensitivity for T13 analyses (66.37–100.00%). The specificities were >99% for each trisomy (99.7% (99.01–99.97%) for T21; 99.5% (98.62–99.85%) for T18; 99.7% (99.03–99.97%) for T13), along with a first-pass no-call rate of 0.93%. Conclusions: The study showed that using a rolling-circle replication-based cfDNA system for the evaluation of the common aneuploidies would provide greater accuracy and clinical utility compared to conventional biochemical screening, and it would provide comparable results to other reported cfDNA methodologies.

【 授权许可】

Unknown