Presymptomatic Identification of Cancers in Pregnant Women During Noninvasive Prenatal Testing

TLDR

Noninvasive prenatal testing (NIPT) uses cell‑free fetal DNA in maternal plasma to screen for fetal aneuploidy, and tumor DNA can similarly be detected and characterized from the same plasma source. This study aims to show that plasma DNA profiling during routine NIPT can detect maternal tumors before symptoms appear. The authors sequenced maternal plasma cfDNA from over 4,000 pregnancies, identifying three aberrant genome‑representation profiles that could not be explained by maternal or fetal genetics. The three patients were diagnosed with ovarian carcinoma, follicular lymphoma, and Hodgkin lymphoma after imaging and biopsy, and the tumor copy‑number profiles matched the NIPT data, demonstrating that NIPT can enable accurate presymptomatic detection and treatment of maternal cancers during pregnancy.

Abstract

Noninvasive prenatal testing (NIPT) for fetal aneuploidy by scanning cell-free fetal DNA in maternal plasma is rapidly becoming a major prenatal genetic test. Similar to placental DNA, tumor DNA can be detected in the plasma, and analysis of cell-free tumor DNA can be used to characterize and monitor cancers. We show that plasma DNA profiling allows for presymptomatic detection of tumors in pregnant women undergoing routine NIPT.During NIPT in over 4000 prospective pregnancies by parallel sequencing of maternal plasma cell-free DNA, 3 aberrant genome representation (GR) profiles were observed that could not be attributed to the maternal or fetal genomic constitution. A maternal cancer was suspected, and those 3 patients were referred for whole-body diffusion-weighted magnetic resonance imaging, which uncovered an ovarian carcinoma, a follicular lymphoma, and a Hodgkin lymphoma, each confirmed by subsequent pathologic and genetic investigations. The copy number variations in the subsequent tumor biopsies were concordant with the NIPT plasma GR profiles.We show that maternal plasma cell-free DNA sequencing for noninvasive prenatal testing also may enable accurate presymptomatic detection of maternal tumors and treatment during pregnancy.