1 Department of Breast Surgery, Zhuhai Hospital of Traditional Chinese and Western Medicine (The Second People's Hospital of Zhuhai) , Zhuhai City, Guangdong, People's Republic of China .
2 Department of Breast Surgery, Nanfang Hospital, Southern Medical University , Guangzhou, Guangdong, People's Republic of China .
DNA Cell Biol. 2018 Jul;37(7):626-633. doi: 10.1089/dna.2017.4112. Epub 2018 Jun 29.
Massively parallel sequencing of circulating fetal DNA in the plasma of pregnant women is a common method for noninvasive prenatal testing (NIPT) of fetal trisomy 13, 18, and 21. However, circulating DNA is not restricted to pregnant women, with increased levels of plasma DNA also frequently detected in the plasma of cancer patients. Among pregnant women whose NIPT results were inconsistent with the fetal karyotype, a small number of patients have subsequently been diagnosed with a previously undetected malignancy. However, the extent to which circulating tumor DNA (ctDNA) affects the results of NIPT is still unclear. We examined serum from 50 nonpregnant women with breast tumors by NIPT. These samples were then added to serum containing trisomy 13, 18, and 21 fetal DNA to figure out the extent to which maternal tumors can interrupt NIPT results in pregnant women with breast tumors. Concentrations of cell-free DNA (cfDNA) were higher in both pregnant women and breast tumor patients, relative to nonpregnant healthy controls. Among the 50 samples evaluated, 3 produced false positive NIPT results for trisomy 13, 18, or 21, indicating that genomic copy number variations (CNVs) had occurred. Simulation testing also showed that ctDNA can increase the standard deviation of the associated z-scores, which lower absolute z-scores by decreasing the proportion of circulating fetal DNA relative to total DNA. Of the 50 samples tested, 9 fell within the equivocal range and 8 produced false negative results for trisomy 13, 18, or 21. Data presented here show for the first time that ctDNA is able to affect NIPT results in two ways. First, ctDNA can lead to false positive results due to the detection of genomic CNVs in tumor DNA. Alternatively, ctDNA can increase the likelihood of a false negative by decreasing the proportion of circulating fetal DNA in serum.
对孕妇血浆中的循环胎儿 DNA 进行大规模平行测序是一种常见的方法,用于非侵入性产前检测(NIPT)胎儿三体 13、18 和 21。然而,循环 DNA 并不仅限于孕妇,癌症患者的血浆中也经常检测到较高水平的血浆 DNA。在 NIPT 结果与胎儿核型不一致的孕妇中,少数患者随后被诊断出先前未检测到的恶性肿瘤。然而,循环肿瘤 DNA(ctDNA)对 NIPT 结果的影响程度仍不清楚。我们通过 NIPT 检查了 50 名非怀孕的乳腺癌患者的血清。然后,将这些样本添加到含有三体 13、18 和 21 胎儿 DNA 的血清中,以确定母体肿瘤在多大程度上可以中断乳腺癌孕妇的 NIPT 结果。与非怀孕的健康对照组相比,孕妇和乳腺癌患者的游离细胞 DNA(cfDNA)浓度更高。在评估的 50 个样本中,有 3 个产生了三体 13、18 或 21 的假阳性 NIPT 结果,表明基因组拷贝数变异(CNVs)已经发生。模拟测试还表明,ctDNA 可以增加相关 z 分数的标准偏差,通过降低循环胎儿 DNA 相对于总 DNA 的比例降低绝对 z 分数。在测试的 50 个样本中,有 9 个处于可疑范围,8 个对三体 13、18 或 21 产生假阴性结果。这里呈现的数据首次表明,ctDNA 能够以两种方式影响 NIPT 结果。首先,ctDNA 可以通过检测肿瘤 DNA 中的基因组 CNVs 导致假阳性结果。或者,ctDNA 可以通过降低血清中循环胎儿 DNA 的比例增加假阴性的可能性。
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