multiplexed maternal plasma DNA sequencing; cell-free DNA aneuploidy screening (cfDNA)
Jump to navigation
Jump to search
Indications
- identification of fetal genetic disease*, including
- 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]
More general terms
More specific terms
Additional terms
References
- ↑ 1.0 1.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21224326 <Internet> http://www.bmj.com/content/342/bmj.c7401.full
- ↑ Chiu RWK, Cantor CR, Lo YMD. Non-invasive prenatal diagnosis by single molecule counting technologies. Trends Genet 2009;25:324-31 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19540612
- ↑ 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23744626 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23744609 <Internet> http://onlinelibrary.wiley.com/doi/10.1002/uog.12504/full - ↑ 4.0 4.1 Bianchi DW et al. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med 2014 Feb 27; 370:799. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24571752 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24571760 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1401129 - ↑ 5.0 5.1 5.2 Norton ME et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med 2015 Apr 2 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25830321 <Internet> 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: https://www.ncbi.nlm.nih.gov/pubmed/25830323 - ↑ Thierry AR et al. Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA. Nat Med 2014 Apr; 20:430 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24658074 <Internet> http://www.nature.com/nm/journal/v20/n4/full/nm.3511.html
- ↑ 7.0 7.1 Amant F et al Presymptomatic Identification of Cancers in Pregnant Women During Noninvasive Prenatal Testing. JAMA Oncol. Published online June 05, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26355862 <Internet> http://oncology.jamanetwork.com/article.aspx?articleid=2318964
- ↑ 8.0 8.1 8.2 8.3 8.4 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