Baylor College of Medicine's department of molecular and human genetics continues to work towards developing a noninvasive version of its chromosomal microarray analysis offering, but the launch of such a test, even for research, could still be years away, according to department chair Arthur Beaudet.
Beaudet told BioArray News this week that it is Baylor's "complete focus" to get a noninvasive version of CMA to work, largely to overcome the perceived shortcomings of existing approaches, as the current CMA relies on samples obtained invasively, while cell-free, next-generation-sequencing-based noninvasive prenatal tests are not comprehensive enough.
Indeed, that was the message of a presentation given by BCM's Amy Breman at the American Society of Human Genetics annual meeting in Boston in October. Breman, a clinical cytogeneticist, said that "while cell-free NIPT has represented a major improvement in prenatal screening, the current methods do not detect many severe disorders."
It is for this reason that there is a "great need for any NIPT test to detect anything that an invasive test might detect," she said, offering up cell-based NIPT using chromosomal microarray analysis as one possible solution.
In her presentation, Breman discussed a Baylor study that compared three single-cell whole genome amplification methods for detection of genomic aberrations by CMA, calling the effort a "step towards noninvasive prenatal diagnosis using intact fetal cells."
She noted that Baylor geneticists had shown in a paper last year that CMA on whole-genome amplification DNA from a single cell could detect copy number changes larger than one megabase using a custom array with focused regions of increased probe coverage.
In the study, the group used Agilent Technologies microarrays to analyze cells from lymphoblastoid cell lines carrying various genomic abnormalities. For whole-genome amplification, the team used multiple methodologies, obtaining data that suggested that aneuploidy and other genomic imbalances in a single cell could be detected by CMA when the amplification, purification, and hybridization conditions were optimized, but that increased probe density may be necessary to consistently detect small copy number changes.
While newer amplification methods may make such a test technically feasible, Beaudet said that the major hindrance to developing noninvasive CMA is problems with extracting whole cells from maternal plasma.
"The technology is better than ever before, but I think the jury is out until cell isolation technology progresses," Beaudet said, adding that some NIPT companies — though he didn't name any specific ones — have portrayed noninvasive CMA as an impossibility because of such bottlenecks.
"They may well be right in the end," Beaudet said, but noted that an array-based alternative, should it become operable, would be "undoubtedly better than what exists now" in terms of NIPT offerings.
"I spend a lot of my day trying to make it happen," Beaudet said of noninvasive CMA, "and I hope it happens sooner than later, but I just can't make a reliable prediction as to when it could become available now," he said.
He added that the study discussed by Breman at ASHG will likely find its way into publication sometime next year.