Prenatal exposure to chemotherapy increases the mutation burden in human neonatal hematopoietic stem cells

Menée à partir du séquençage de l'ADN de cellules progénitrices et de cellules souches hématopoïétiques extraites de sang de cordon ombilical prélevé sur des femmes enceintes traitées ou non pour un cancer (sein, col de l'utérus ou lymphome hodgkinien), cette étude met en évidence l'impact d'une exposition prénatale à une chimiothérapie sur la charge mutationnelle des cellules souches hématopoïétiques néonatales

Résumé en anglais

Chemotherapy is included in the standard of care for cancer treatment during pregnancy. However, whether prenatal exposure to maternal chemotherapy treatment has a mutagenic impact on the fetal genome, remains unexplored. Therefore, we investigated mutation accumulation in hematopoietic stem and progenitor cells (HSPCs) from neonates born to pregnant cancer patients treated with chemotherapy, as well as healthy pregnant women and untreated pregnant cancer patients. The mutational burden in HSPCs from neonates born to untreated pregnant cancer patients and to healthy controls was similar, but increased after prenatal exposure to varying types of chemotherapy regimens. Mutational signature analyses attributed the excess mutations to clock-like processes, which are active during normal cellular aging, or to direct mutagenesis by platinum-based drugs in neonates prenatally exposed to platinum-containing regimens. Our findings in the neonatal hematopoietic compartment are consistent with mutational signatures previously identified in cells of cancer survivors directly exposed to these chemotherapeutic drugs.