GMDxCo Pty Ltd, Melbourne, Victoria, Australia; Department of Animal, Plant and Soil Sciences, La Trobe University, Melbourne, Victoria, Australia.
GMDxCo Pty Ltd, Melbourne, Victoria, Australia; Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Monash University, Clayton, Victoria, Australia.
Mutat Res. 2020 May-Dec;821:111705. doi: 10.1016/j.mrfmmm.2020.111705. Epub 2020 May 18.
Somatic mosaicism is a normal occurrence during development in the tissues and organs. As part of establishing a "healthy population "(HP) background or base-line, we investigated whether such mosaicism can be routinely detected in the circulating DNA secured from a rigorously designed healthy human liquid biopsy clinical trial (saliva, blood). We deployed next generation (NG) whole exome sequencing (WES) at median exome coverage rates of 97.2 % (-to-30x) and 70.0 % (-to-100x). We found that somatic mosaicism is not detectable by such standard bulk WES sequencing assays in saliva and blood DNA in 24 normal healthy Caucasians of both sexes from 18 to 60 years of age. We conclude that for circulating DNA using standard WES no novel somatic mutational variants can be detected in protein-coding regions of normal healthy subjects. This implies that the extent within normal tissues of somatic mosaicism must be at a lower level, below the detection threshold, for these circulating DNA WES read depths.
体细胞嵌合是组织和器官发育过程中的一种正常现象。作为建立“健康人群”（HP）背景或基线的一部分，我们研究了在严格设计的健康人类液体活检临床试验（唾液、血液）中获得的循环 DNA 中是否可以常规检测到这种嵌合体。我们部署了下一代（NG）全外显子组测序（WES），中位外显子覆盖率为 97.2%（-至-30x）和 70.0%（-至-100x）。我们发现，在 24 名年龄在 18 至 60 岁的两性正常白种人中，唾液和血液 DNA 中的体细胞嵌合通过这种标准的 bulk WES 测序检测不到。我们的结论是，对于使用标准 WES 的循环 DNA，在正常健康受试者的蛋白质编码区域中不能检测到新的体细胞突变变体。这意味着，对于这些循环 DNA WES 读取深度，正常组织内体细胞嵌合体的程度必须低于检测阈值。
