ADN Fœtal Circulant, Grossesse et Pathologies Malignes

In France in 2021, 90% of pregnant women chose to undergo screening for Trisomy 21, and 128,958 women benefited from a fetal aneuploidy screening test based on the analysis of cell-free DNA (cfDNA) in maternal blood. At the beginning of its use, this analysis was limited to screening for Trisomy 21, but it now allows the study of all chromosomes (expanded screening). More than half of fetal chromosomal abnormality screenings are expanded tests, and this practice continues to grow. In oncology, circulating tumor DNA (ctDNA) is studied for the detection, prognostic evaluation, and monitoring of the effectiveness of certain treatments. The high-throughput sequencing tools used for aneuploidy screening during pregnancy are likely to detect malignant diseases. Cancer is associated with pregnancy in 1 in 1,000 to 1 in 1,500 pregnant women, and the spread of expanded aneuploidy screening during pregnancy makes it possible to detect maternal cancers, including at infraclinical stages. This study will therefore help manage situations involving difficult-to-interpret results, such as suspected maternal cancer. It will make it possible to identify specific chromosomal abnormalities to be tested, which could potentially be included in future recommendations. In a second stage, it could contribute to harmonizing the practices of laboratory specialists performing fetal chromosomal abnormality screening using cfDNA.

Cancer is associated with pregnancy in 1 in 1,000 to 1 in 1,500 pregnant women,¹² but the estimated incidence varies depending on whether cancers pre-existing before pregnancy, cancers diagnosed during pregnancy, and sometimes those discovered in the postpartum period are included. The cancers most frequently encountered in the context of pregnancy are breast cancer, cervical cancer, melanoma, and thyroid cancer. In 2015, D. Bianchi's team⁵ was the first to report the possibility of incidentally detecting cancers in pregnant women during the analysis of circulating cell-free DNA (cfDNA) performed for fetal chromosomal abnormality screening. In a cohort of 125,426 tests, 10 maternal cancers were identified. Since then, around one hundred cases have been reported, most often as case reports or small series.³ Maternal cancer may be suspected when the cfDNA test result (performed for trisomies 21, 18, and 13, or as part of expanded screening) shows either multiple chromosomal abnormalities or an abnormality known to be associated with a certain type of cancer, such as some lymphomas. In oncology, circulating tumor DNA (ctDNA) is studied for cancer detection, prognostic evaluation, and monitoring the effectiveness of certain treatments. The presence of ctDNA has been known since 1989. It originates from cells of the primary tumor and reflects genetic alterations (copy number variations, somatic mutations, methylation changes, etc.). The amount of ctDNA depends on tumor size, tumor type, cellular turnover, tumor location, and disease stage. ctDNA levels are higher in advanced stages of cancer, but the tumor fraction may remain very low even in cases of metastatic disease.