NIPT genome analysis for predicting cancer


A retrospective analysis has found that comprehensive examination of shallow-sequenced, whole-genome cell-free DNA (cfDNA) allows for the incidental detection of maternal tumors, with relatively high precision.

The Belgium analysis in the journal EClinical Medicine, published by The Lancet, concluded there was a positive predictive value (PPV) of 73% using the noninvasive prenatal testing (NIPT) approach for cancer detection in over 85,000 pregnancies at a single center.

Liesbeth Lenaerts, PhD, a research expert for the Cancer in Pregnancy group within the Department of Oncology at Catholic University Leuven, Belgium, is the first author. She said that her group incidentally identified some occult malignancies in asymptomatic women via routine NIPT at University Hospitals Leuven, and therefore wondered how accurate their NIPT method was for cancer prediction.

The authors also noticed a lack of awareness among caregiving physicians, including genetic counsellors and obstetricians, about the potential aetiologies of aberrant NIPT outcomes. “This in turn can have negative consequences for the management of women confronted with such a deviating NIPT result,” Lenaerts told Contemporary OB/GYN®.

Besides being motivated to increase the general awareness of the link between NIPT and cancer detection, the investigators sought to create a clinical care model that could be implemented by other caregiving physicians to optimize the management of women with a NIPT result that is suspicious of cancer.

A data set of 88,294 NIPT performed at University Hospital Leuven between November 2013 and March 2020 was assessed.

For 15 asymptomatic women, the NIPT result was classified as suggestive of cancer via an unbiased NIPT analysis pipeline known as Genomic Imbalance Profiling from cfDNA SEQuencing (GIPSeq).

The cfDNA profiles of these women showed either genome-wide aberrations or a single trisomy 8.

Upon clinical examination, a solid or hematological cancer was detected in 4 and 7 of the cases, respectively, and 3 of the 15 women were identified as having a clonal mosaicism. In 1 case, no underlying condition was found.

“These numbers translate to a PPV of 73%, which is significantly higher than has been reported in previous large NIPT series for detecting asymptomatic malignancies and using only cfDNA analysis,” Lenaerts said.

The authors were not surprised, though, that haematological malignancies were most frequently identified, followed by detection of breast cancers. “The preponderance of haematological diagnoses by NIPT is plausible when cfDNA is largely derived from hematopoietic cells,” Lenaerts said.

Detecting a malignancy during pregnancy permits the identification of potential obstetric and neonatal risks, according to Lenaerts. “Oncological treatment in pregnancy may also be possible without affecting short-term neonate outcomes,” she said.

Due to the complexity of diagnosing a pregnant woman with cancer, clinical follow-up should occur in a well-designed multidisciplinary setting with appropriate concerted downstream actions.

“However, NIPT should not be considered as a cancer screening test,” Lenaerts said. “Nonetheless, current investigations in the liquid biopsy field of cancer screening are exploiting supramolecular information contained in cfDNA to identify the tissue of origin and guide oncological investigations. In the future, such strategies might be implemented in the obstetrics field.”

The authors strongly advocate institutional or national guidelines for the clinical evaluation of pregnant women suspected of having cancer based on their NIPT outcome.



Lenaerts reports no relevant financial disclosures.


Lenaerts L, Brison N, Maggen C, et al. Comprehensive genome-wide analysis of routine non-invasive test data allows cancer prediction: a single-center retrospective analysis of over 85,000 pregnancies.

EClinicalMedicine. Published online May 13, 2021. doi:10.1016/j.eclinm.2021.100856

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