Fetal DNA from Pap tests?


Trophoblast retrieval and isolation from the cervix (TRIC) may one day lead to early identification of fetal genetic disorders.

Isolation and analysis of trophoblast cells that carry fetal DNA may be possible as early as 5 weeks’ gestation, according to researchers from Wayne State University. Reporting in Science Translational Medicine, they describe results of a small proof-of-concept study of next-generation sequencing of cells obtained noninvasively from Pap smears.

Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the research may lead to clinical trials of the technique, called trophoblast retrieval and isolation from the cervix (TRIC). The next step, says the authors, is to determine whether TRIC can identify genetic disorders in a fetus.

For the proof-of-concept work, the researchers were able to isolate intact trophoblast cells from Pap smears collected noninvasively at 5 to 19 weeks’ gestation for next-generation sequencing of fetal DNA. Profiling of 20 consecutive matched maternal, placental, and fetal samples was performed with multiplex targeted DNA sequencing of 59 short tandem repeat and 94 single-nucleotide variant sites across all 24 chromosomes. The data revealed fetal DNA fractions of 85% to 99.9%, with 100% correct fetal haplotyping with minimal maternal DNA contamination.

“We used next-generation sequencing and accurately determined the nucleotide sequence down to a single base,” said co-principal investigator Sascha Drewlo, PhD, in a press release. “TRIC could be used as a noninvasive test, with the accuracy of invasive tests like amniocentesis, and the ability to perform the test 5 to 10 weeks earlier than current testing modalities.”

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