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multiplexed maternal plasma DNA sequencing; cell-free DNA aneuploidy screening (cfDNA)

Indications: - identification of fetal genetic disease*, including - Down's syndrome - fetal aneuploidy - fetal trisomy - trisomy 13, trisomy 18, trisomy 21 [5] - assessment of fetal sex chromosome composition [8] - screening for early cancers in pregnant women [7] - screening for ovarian cancer - *screening for lymphoma (follicular lymphoma) - *screening for Hodgkin's lymphoma * may eliminate need for amniocentesis in some cases Contraindications: - identification of chromosomal translocations best done through amniocentesis [5] - risk assessment for neural tube or ventral wall defects [8] - risk assessment for microdeletion syndromes - patients with multiple gestation [8] - as a single basis of pregnancy management decisions [8] Principle: - cell-free DNA from the fetus has been found in the plasma of pregnant women - the basis of these tests is the detection of fetal-specific DNA sequences in maternal plasma - fetal-specific nucleic acids, such as DNA methylation & mRNA markers in maternal plasma, has been proposed for detection of fetal aneuploidies Clinical significance: - non-invasive maternal plasma sampling - this test has facilitated determination of fetal sex & fetal RhD genotype in RhD negative women - trisomy 21 fetuses can be detected with 100% sensitivity & 97.9% specificity, with a positive predictive value of 96.6% & a negative predictive value of 100% [1] - also detects trisomy 18 & trisomy 13 Notes: - lower false-positive rates than standard screening for trisomy 21 & trisomy 18 [4]

Related

amniocentesis chorionic villus sampling

Specific

fetal sex in plasma cell-free DNA

General

maternal screen for fetal abnormalities such as open neural tube defects, trisomy 21 or trisomy 18 panel in serum/plasma cell-free (circulating tumor) DNA in plasma (liquid biopsy, cFDNA, ctDNA)

References

  1. Chiu RWK et al Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study BMJ 2011; 342:c7401 PMID: 21224326 http://www.bmj.com/content/342/bmj.c7401.full
  2. Chiu RWK, Cantor CR, Lo YMD. Non-invasive prenatal diagnosis by single molecule counting technologies. Trends Genet 2009;25:324-31 PMID: 19540612
  3. Nicolaides KH et al First-trimester contingent screening for trisomy 21 by biomarkers and maternal blood cell-free DNA testing. Ultrasound in Obstetrics and Gynecology. June 7, 2013 PMID: 23744626 http://onlinelibrary.wiley.com/doi/10.1002/uog.12511/full - Gil MM, Quezada MS, Bregant B Implementation of maternal blood cell-free DNA testing in early screening for aneuploidies Ultrasound in Obstetrics and Gynecology. June 7, 2013 PMID: 23744609 http://onlinelibrary.wiley.com/doi/10.1002/uog.12504/full
  4. Bianchi DW et al. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med 2014 Feb 27; 370:799. PMID: 24571752 http://www.nejm.org/doi/full/10.1056/NEJMoa1311037 - Greene MF and Phimister EG. Screening for trisomies in circulating DNA. N Engl J Med 2014 Feb 27; 370:874 PMID: 24571760 http://www.nejm.org/doi/full/10.1056/NEJMe1401129
  5. Norton ME et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med 2015 Apr 2 PMID: 25830321 http://www.nejm.org/doi/full/10.1056/NEJMoa1407349 - Snyder MW et al. Copy-number variation and false positive prenatal aneuploidy screening results. N Engl J Med 2015 Apr 2 PMID: 25830323
  6. Thierry AR et al. Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA. Nat Med 2014 Apr; 20:430 PMID: 24658074 http://www.nature.com/nm/journal/v20/n4/full/nm.3511.html
  7. Amant F et al Presymptomatic Identification of Cancers in Pregnant Women During Noninvasive Prenatal Testing. JAMA Oncol. Published online June 05, 2015 PMID: 26355862 http://oncology.jamanetwork.com/article.aspx?articleid=2318964
  8. ACOG Committee Opinion. Number 640, September 2015 Cell-free DNA Screening for Fetal Aneuploidy. http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Genetics/Cell-free-DNA-Screening-for-Fetal-Aneuploidy