评估游离DNA中的体细胞突变作为无症状孕妇癌症的无创生物标志物

Prenatal cell-free (cf) DNA sequencing for fetal aneuploidy incidentally detects circulating tumor DNA in the plasma of asymptomatic pregnant women. Distinguishing the subset of women with malignant tumors detected by prenatal sequencing from those with benign conditions, such as uterine fibroids, is critical to maternal medical management. In this pilot study, prospectively collected blood samples from 65 pregnant or postpartum women with and without occult cancers were analyzed blindly for cfDNA somatic mutations in 275 cancer-associated genes. Somatic variants were common among all 65 women, however, when stringent mutation analysis criteria were applied, these data could independently differentiate women with cancer with a sensitivity of 80.6% and specificity of 100%. Mutation profiling complements radiographic imaging by clarifying tumor origin, evaluating malignancy in indeterminate cases, identifying actionable genomic alterations, and flagging high-risk patients for urgent intervention. These findings provide preliminary evidence that cfDNA somatic mutations could serve as an additional noninvasive biomarker of malignancy potentially aiding the management of women with prenatal cfDNA findings suspicious for cancer.