Photo by Nina Matthews
Researchers have again found evidence to suggest that tests used to identify chromosomal fetal disorders can detect occult malignancies in pregnant women.
In a study made public last month, non-invasive prenatal tests (NIPTs) revealed 2 cases of lymphoma and a case of ovarian cancer in expectant mothers.
In the new study, researchers showed that positive NIPT results were due to leukemia, lymphoma, or solid tumors in 10 expectant mothers.
The research was published in JAMA and presented at the 19th International Conference on Prenatal Diagnosis and Therapy in Washington, DC. Funding for the study was provided by Illumina, and company employees were involved in the research.
“We did this study because noninvasive prenatal testing using sequencing of cell-free DNA in the mother’s plasma is the fastest-growing area of prenatal testing and, indeed, of genomic medicine,” said study author Diana W. Bianchi, MD, of Tufts Medical Center in Boston, Massachusetts.
“As the volume of tests has expanded, we’ve become increasingly aware of the so-called “false-positive” cases. [A]pproximately 0.2% of the time, there is a discrepancy between the results of the prenatal test—in which an aneuploidy is reported—and the result from the diagnostic fetal procedure, the amniocentesis or the chorionic villus sampling.”
“So we’re interested in the situation where the fetal chromosomes are normal, but the prenatal test shows that there’s an aneuploidy detected. We’re interested in the possible explanations for that discrepancy.”
To gain some insight, Dr Bianchi and her colleagues evaluated 125,426 samples from asymptomatic pregnant women who underwent plasma cell-free DNA sequencing for clinical prenatal aneuploidy screening using Illumina’s verifi Prenatal Test.
In all, 3757 samples (3%) were positive for 1 or more aneuploidies involving chromosomes 13, 18, 21, X, or Y. These were reported to the ordering physician with recommendations for further evaluation.
“In a small minority of women, [subsequent tests analyzing only fetal DNA] showed that the fetal chromosomes were normal, and that disagreed with [results of the NIPT],” Dr Bianchi said. “We were examining whether cancer could explain the discrepancy between these two test results.”
The researchers found that 10 of the women with discordant test results were subsequently diagnosed with cancer. There were 3 cases of B-cell lymphoma and 1 case each of T-cell leukemia, Hodgkin lymphoma, unspecified adenocarcinoma, leiomyosarcoma, and neuroendocrine, colorectal, and anal carcinomas.
Dr Bianchi and her colleagues were able to obtain detailed clinical and sequencing data for 8 of these cases. In the other 2 cases (leiomyosarcoma and unspecified adenocarcinoma), the women were critically ill and were not approached about participating in the study.
The researchers found that maternal cancers most frequently occurred when the NIPT detected more than 1 aneuploidy. There were 7 known cancers among 39 cases of multiple aneuploidies by NIPT. In 1 case, blood was sampled after the patient completed treatment for colorectal cancer, and the abnormal pattern was no longer evident.
When the researchers examined additional genetic information for the women with cancer, they found unique patterns of nonspecific copy-number gains and losses across multiple chromosomes.
“[These women] had DNA imbalances all across the genome,” Dr Bianchi said. “The [NIPT] normally is only looking at DNA material from the chromosomes of clinical interest—chromosomes 13, 18, 21, X, and Y.”
“When we opened up their results to look at all of the chromosomes, there were multiple abnormalities in other places, such as chromosome 8, chromosome 6, etc. Each woman had a unique pattern that was abnormal in many places. This suggested that it was the tumor DNA that was being shed into her blood and was contributing to the abnormal pattern.”
Dr Bianchi stressed that the tumor DNA did not affect the babies. She said all were born healthy, although labor was induced early in one mother to facilitate her cancer treatment.
