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Researchers from Wayne State University in Detroit reported in Science Translational Medicine the results of a small proof-of-concept study suggesting that analyzing fetal DNA collected from Papanicolaou (Pap) smears could lead to earlier prenatal screening. The novel noninvasive method involves collecting trophoblast cells for DNA analysis.
Amniocentesis and chorionic villus sampling, which are currently used to identify chromosomal abnormalities, carry a small risk of miscarriage. Cell-free fetal DNA testing, while not invasive, still requires verification by invasive tests. All are performed toward the end of the first trimester or later.
The researchers developed a procedure using the Pap smear to capture enough intact fetal trophoblast cells for next-generation sequencing as early as 5 weeks into the pregnancy. These trophoblast cells naturally migrate into the reproductive tract. However, they have not been used for DNA analysis because of the low cell recovery and excess maternal cells in the specimens.
The researchers previously demonstrated a method of purifying the fetal cells using trophoblast retrieval isolation from the cervix (TRIC). In this study, they isolated the cells from 20 women at 5 to 19 weeks’ pregnancy, retrieving an average of 282 trophoblast cells from each. After assessing the purity of the cells, separating out the maternal cells, and comparing the DNA with the mother’s genes and DNA from the placenta, they used nuclear isolation combined with DNase treatment after TRIC for the fetal trophoblast cells to ensure high-quality DNA samples. They then used next-generation sequencing to accurately determine the nucleotide sequence down to a single base.
“TRIC could be used as a noninvasive test with the accuracy of invasive tests like amniocentesis and the ability to perform the test five to 10 weeks earlier than current testing modalities," concluded one of the two lead authors, Sascha Drewlo, PhD, an associate professor of obstetrics and gynecology at Wayne State, in a statement.
The researchers are now planning clinical trials to determine if TRIC can identify genetic disorders in the fetus using next-generation proteomics and transcriptomics approaches. They also want to learn more about the cells obtained through TRIC, including their origins and relationship to their counterparts that remain in the placenta.