NEW YORK (GenomeWeb) – Noninvasive prenatal testing for fetal chromosomal abnormalities can occasionally have the unexpected consequence of identifying malignancies in the expecting mom, according to a study published today in JAMA Oncology that will also be presented at the European Society for Human Genetics meeting in London.
Although rare, researchers at the University of Leuven in Belgium reported that out of 4,000 noninvasive prenatal tests ran in prospective pregnancies, three yielded aberrant genome representations that were confirmed to be maternal cancer.
Such testing "may enable accurate presymptomatic detection of maternal tumors and treatment during pregnancy," the authors wrote.
Previous studies have also reported that false positive or unclear NIPT results are sometimes due to maternal malignancies. For instance, in a 2013 study published in Prenatal Diagnosis, researchers published a case example of a woman whose NIPT result indicated a fetus aneuploidy in chromosome 13 and 18, but the result of the noninvasive test could not be confirmed via amniocentesis, or subsequent ultrasound testing. Cancer was not diagnosed until after the woman gave birth. At this year's Future of Genomic Medicine conference in San Diego, a woman spoke of her experience of an abnormal NIPT result leading to an eventual diagnosis of colorectal adenocarcinoma.
In the JAMA Oncology study, however, the researchers reported that rather than getting false positive or unclear NIPT results, test analyses could be tweaked so "the interrogation of segmental aneuploidies genome-wide could not only avoid false-positive assignment of fetal aneuploidy due to the presence of a maternal cancer but, more importantly, enable identification of the imbalances as cancer-derived anomalies."
In their study of 4,000 women undergoing NIPT testing, they identified three cases of cancer, a frequency consistent with what would be expected based on the known prevalence of cancer in the general population.
NIPT revealed three profiles that had an "aberrant quality score" and "genome-wide representation profiles reminiscent of cancer-related copy number variation," the authors wrote. All three women were referred for whole-body MRI scans, and in all cases a tumorous mass was found, including one case of bilateral ovarian carcinoma with multiple metastases, one of follicular lymphoma, and one of Hodgkin lymphoma. Array CGH or FISH testing confirmed the genomic findings of the cell-free DNA test — indicating that even though NIPT was not designed to detect tumors, it is specific for doing so, the authors wrote.
In the case of the woman diagnosed with Hodgkin lymphoma, the Leuven team has since gone on to develop a blood test for the disease that analyzes circulating cell-free DNA.
Two out of the three patients diagnosed in the JAMA Oncology study underwent successful treatment. The patient with ovarian cancer waited until after delivery, while the patient with Hodgkin lymphoma was treated during her pregnancy without complications to her or her fetus and gave birth to a healthy girl. The patient with follicular lymphoma did not undergo treatment, since it was slow growing and may not require therapy for years.
The researchers said that their study indicates that NIPT analysis could provide added value by identifying maternal malignancies, and that additional studies addressing the impact of looking for such entities should be conducted.
"Since cancer-related symptoms may be masked, especially during pregnancy, we consider the presymptomatic identification of maternal cancer as a potential added value of NIPT," they wrote. And indeed, Eunice Lee, who spoke at the Future of Genomic Medicine conference on the experience of her NIPT result leading to an early cancer diagnosis, said she was lucky, since the early diagnosis meant she was able to be treated early and is so far cancer-free.