Prenatal cfDNA Sequencing and Incidental Detection of Maternal Cancer

作者：Amy Turriff, Christina M. Annunziata, Ashkan A. Malayeri, Bernadette Redd, Miroslava Pavelova, Ian S. Goldlust, Padma Sheila Rajagopal, Jielu Lin, Diana W. Bianchi · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2401029 · 被引用次数：45 · 研究领域：Prenatal Screening and Diagnostics、Cancer Genomics and Diagnostics、Cancer Risks and Factors

BACKGROUND: Cell-free DNA (cfDNA) sequence analysis to screen for fetal aneuploidy can incidentally detect maternal cancer. Additional data are needed to identify DNA-sequencing patterns and other biomarkers that can identify pregnant persons who are most likely to have cancer and to determine the best approach for follow-up. METHODS: In this ongoing study we performed cancer screening in pregnant or postpartum persons who did not perceive signs or symptoms of cancer but received unusual clinical cfDNA-sequencing results or results that were nonreportable (i.e., the fetal aneuploidy status could not be assessed) from one of 12 different commercial laboratories in North America. We used a uniform cancer-screening protocol including rapid whole-body magnetic resonance imaging (MRI), laboratory tests, and standardized cfDNA sequencing for research purposes with the use of a genomewide platform. The primary outcome was the presence of cancer in participants after the initial cancer-screening evaluation. Secondary analyses included test performance. RESULTS: Cancer was present in 52 of the 107 participants in the initial cohort (48.6%). The sensitivity and specificity of whole-body MRI in detecting occult cancer were 98.0% and 88.5%, respectively. Physical examination and laboratory tests were of limited use in identifying participants with cancer. Research sequencing showed that 49 participants had a combination of copy-number gains and losses across multiple (≥3) chromosomes; ca...