Plasma placental RNA allelic ratio permits noninvasive prenatal chromosomal aneuploidy detection

Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, 00, Hong Kong
Nature Medicine (Impact Factor: 28.05). 03/2007; 13(2):218-23. DOI: 10.1038/nm1530
Source: PubMed

ABSTRACT Current methods for prenatal diagnosis of chromosomal aneuploidies involve the invasive sampling of fetal materials using procedures such as amniocentesis or chorionic villus sampling and constitute a finite risk to the fetus. Here, we outline a strategy for fetal chromosome dosage assessment that can be performed noninvasively through analysis of placental expressed mRNA in maternal plasma. We achieved noninvasive prenatal diagnosis of fetal trisomy 21 by determining the ratio between alleles of a single-nucleotide polymorphism (SNP) in PLAC4 mRNA, which is transcribed from chromosome 21 and expressed by the placenta, in maternal plasma. PLAC4 mRNA in maternal plasma was fetal derived and cleared after delivery. The allelic ratios in maternal plasma correlated with those in the placenta. Fetal trisomy 21 was detected noninvasively in 90% of cases and excluded in 96.5% of controls.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: The non-invasive identification of epidermal growth factor receptor (EGFR) mutations is important for the institution of individualized therapy of non-small cell lung cancer (NSCLC). In this study, the feasibility of screening for EGFR exon 19 E746_A750del mutations in circulating DNA from plasma was assessed. Methods: Mutant-specific primers with a Taqman probe (MST-PCR) were designed. The ability of this method to accurately detect decreasing concentrations of E746_A750del mutant within a wild type DNA background that mimics the situation of a plasma sample from patients with acquired mutations is verified. To verify the clinical applicability of this method, 55 plasma samples from NSCLC patients were tested, and the sensitivity of MST-PCR was compared to that of direct sequencing. Results: The results showed that MST-PCR could detect 10 to 50 copies/mu L of E746_A750del, representing 0.1% of the wild type EGFR allelic population. Among the 55 cases of NSCLC, 10 cases of E746_A750del were detected by MST-PCR, while only 1 case was revealed by direct sequencing. Conclusions: These findings demonstrate that MST-PCR provides superior sensitivity for the detection of the E746_A750del mutation, suggesting its potential application in the noninvasive detection of E746_A750del mutations in plasma samples from NSCLC patients.
    Clinical laboratory 01/2014; 60(9):1517-26. DOI:10.7754/Clin.Lab.2014.140106 · 1.08 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 1. PSA in Screening for Prostate Cancer: More Good than Harm or More Harm than Good? 2. Ovarian Cancer Biomarkers: Current State and Future Implications from High-Throughput Technologies 3. Procollagen Assays in Cancer 4. Metabolomics in Dyslipidemia 5. Metabolism in Chronic Fatigue Syndrome 6. Cellular Regulation of Glucose Uptake by Glucose Transporter GLUT4 7. Identifying and Reducing Potentially Wrong Immunoassay Results Even When Plausible and “Not-Unreasonable”
    Advances in clinical chemistry 04/2014; 66:1-294. · 4.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: recent studies have proposed the introduction of cell-free fetal DNA testing (NIPT-Non Invasive Prenatal Testing) in routine clinical practice emphasizing its high sensibility and specificity. In any case, false positive and false negative findings may result from placental mosaicism, because cell-free fetal DNA originates mainly from placenta.


Available from