Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
Proc Natl Acad Sci U S A. 2020 Mar 3;117(9):4858-4863. doi: 10.1073/pnas.1910041117. Epub 2020 Feb 19.
We report a sensitive PCR-based assay called Repetitive Element AneupLoidy Sequencing System (RealSeqS) that can detect aneuploidy in samples containing as little as 3 pg of DNA. Using a single primer pair, we amplified ∼350,000 amplicons distributed throughout the genome. Aneuploidy was detected in 49% of liquid biopsies from a total of 883 nonmetastatic, clinically detected cancers of the colorectum, esophagus, liver, lung, ovary, pancreas, breast, or stomach. Combining aneuploidy with somatic mutation detection and eight standard protein biomarkers yielded a median sensitivity of 80% in these eight cancer types, while only 1% of 812 healthy controls scored positive.
我们报告了一种灵敏的基于 PCR 的分析方法，称为重复元件非整倍性测序系统（RealSeqS），它可以在含有少至 3pg DNA 的样本中检测非整倍性。使用单个引物对，我们扩增了分布在整个基因组中的约 35 万个扩增子。在总共 883 例非转移性、临床检测到的结直肠、食管、肝、肺、卵巢、胰腺、乳腺或胃的癌症的液体活检中，有 49%检测到了非整倍性。将非整倍性与体细胞突变检测和 8 种标准蛋白质生物标志物相结合，在这 8 种癌症类型中获得了 80%的中位敏感性，而 812 例健康对照中只有 1%呈阳性。
