Belic Jelena, Koch Marina, Ulz Peter, Auer Martina, Gerhalter Teresa, Mohan Sumitra, Fischereder Katja, Petru Edgar, Bauernhofer Thomas, Geigl Jochen B, Speicher Michael R, Heitzer Ellen
Institute of Human Genetics, Medical University of Graz, Graz, Austria.
Institute of Molecular Biotechnology, Technical University of Graz, Graz, Austria.
Adv Exp Med Biol. 2016;924:147-155. doi: 10.1007/978-3-319-42044-8_28.
Recent progress in the analysis of cell-free DNA fragments (cell-free circulating tumor DNA, ctDNA) now allows monitoring of tumor genomes by non-invasive means. However, previous studies with plasma DNA from patients with cancer demonstrated highly variable allele frequencies of ctDNA. Comprehensive genome-wide analysis of tumor genomes is greatly facilitated when plasma DNA has increased amounts of ctDNA. In order to develop a fast and cost-effective pre-screening method for the identification of plasma samples suitable for further extensive qualitative analysis, we adapted the recently described FAST-SeqS method. We show that our modified FAST-SeqS method (mFAST-SeqS) can be used as a pre-screening tool for an estimation of the ctDNA percentage. Moreover, since the genome-wide mFAST-SeqS z-scores correlate with the actual tumor content in plasma samples, changes in ctDNA levels associated with response to treatment can be easily monitored without prior knowledge of the genetic composition of tumor samples.
游离DNA片段（游离循环肿瘤DNA，ctDNA）分析方面的最新进展使得通过非侵入性手段监测肿瘤基因组成为可能。然而，先前对癌症患者血浆DNA的研究表明，ctDNA的等位基因频率高度可变。当血浆DNA中ctDNA含量增加时，肿瘤基因组的全基因组综合分析会得到极大促进。为了开发一种快速且经济高效的预筛选方法，以鉴定适合进一步进行广泛定性分析的血浆样本，我们采用了最近描述的FAST-SeqS方法。我们表明，我们改良的FAST-SeqS方法（mFAST-SeqS）可作为一种预筛选工具来估计ctDNA百分比。此外，由于全基因组mFAST-SeqS z分数与血浆样本中的实际肿瘤含量相关，因此无需事先了解肿瘤样本的基因组成，就可以轻松监测与治疗反应相关的ctDNA水平变化。
