Goldlust Ian S, Bianchi Diana W
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
Prenatal Genomics and Therapy Section, Center for Precision Health Research, National Human Genome Institute, National Institutes of Health, Bethesda, MD, United States.
Clin Chem. 2025 Jan 3;71(1):61-68. doi: 10.1093/clinchem/hvae170.
Prenatal cell-free DNA (cfDNA) screening is a success story of clinical genomics that has translated to and transformed obstetric care. It is a highly sensitive and specific method of screening for the most common fetal aneuploidies, including trisomies 13, 18, and 21. While primarily designed to detect fetal chromosomal abnormalities, the test also analyzes maternal cfDNA, which can complicate interpretation of results. Occasionally, abnormalities in cfDNA that do not align with fetal aneuploidy may indicate benign or malignant maternal disease states, presenting unique diagnostic challenges and opportunities.
This review explores the methods and implications of incidental cancer detection through prenatal cfDNA screening. Early case reports noted instances in which abnormal cfDNA results, initially suggestive of fetal aneuploidies, led to post-pregnancy diagnoses of maternal cancers. Subsequent large retrospective studies have established significant correlations between atypical prenatal cfDNA results and undiagnosed maternal malignancies. Abnormal cfDNA profiles, particularly those indicating multiple aneuploidies, first require fetal diagnostic tests, such as amniocentesis. If the fetal studies are normal, further investigation into a maternal source should proceed. Clinical management of these findings may involve a multidisciplinary approach, incorporating advanced imaging techniques and genetic counseling to ensure timely and accurate maternal diagnoses.
The integration of genome-wide analysis and innovative bioinformatics tools into prenatal cfDNA screening has enhanced its ability to identify potential cancer cases. Developing standardized guidelines for reporting and managing incidental findings is crucial to optimizing patient outcomes and mitigating psychological impacts on expectant persons and their partners.
产前游离DNA（cfDNA）筛查是临床基因组学的一个成功案例，已转化并改变了产科护理。它是一种高度敏感和特异的方法，用于筛查最常见的胎儿非整倍体，包括13、18和21三体。虽然该检测主要旨在检测胎儿染色体异常，但它也会分析母体cfDNA，这可能会使结果的解读变得复杂。偶尔，与胎儿非整倍体不相符的cfDNA异常可能表明母体患有良性或恶性疾病，带来了独特的诊断挑战和机遇。
本综述探讨了通过产前cfDNA筛查意外发现癌症的方法及影响。早期病例报告指出，一些异常cfDNA结果最初提示胎儿非整倍体，但最终导致产后诊断出母体癌症。随后的大型回顾性研究已证实非典型产前cfDNA结果与未诊断出的母体恶性肿瘤之间存在显著相关性。异常的cfDNA图谱，尤其是那些表明存在多种非整倍体的图谱，首先需要进行胎儿诊断检测，如羊膜穿刺术。如果胎儿检测结果正常，则应进一步调查母体来源。这些发现的临床管理可能需要多学科方法，包括先进的成像技术和遗传咨询，以确保及时、准确地诊断母体疾病。
将全基因组分析和创新的生物信息学工具整合到产前cfDNA筛查中，增强了其识别潜在癌症病例的能力。制定报告和管理意外发现的标准化指南对于优化患者预后以及减轻对准父母及其伴侣的心理影响至关重要。
