Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA.
Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, USA.
Genome Biol. 2024 Jun 14;25(1):157. doi: 10.1186/s13059-024-03262-2.
Methylation-based liquid biopsies show promises in detecting cancer using circulating cell-free DNA; however, current limitations impede clinical application. Most assays necessitate substantial DNA inputs, posing challenges. Additionally, underrepresented tumor DNA fragments may go undetected during exponential amplification steps of traditional sequencing methods. Here, we report linear amplification-based bisulfite sequencing (LABS), enabling linear amplification of bisulfite-treated DNA fragments in a genome-wide, unbiased fashion, detecting cancer abnormalities with sub-nanogram inputs. Applying LABS to 100 patient samples revealed cancer-specific patterns, copy number alterations, and enhanced cancer detection accuracy by identifying tissue-of-origin and immune cell composition.
基于甲基化的液体活检技术在利用循环游离 DNA 检测癌症方面显示出了前景，但目前的局限性阻碍了其临床应用。大多数检测方法需要大量的 DNA 输入，这带来了挑战。此外，在传统测序方法的指数扩增步骤中，可能会遗漏代表性不足的肿瘤 DNA 片段。在这里，我们报告了基于线性扩增的亚硫酸氢盐测序（LABS），该方法能够以全基因组、无偏倚的方式对亚硫酸氢盐处理的 DNA 片段进行线性扩增，以亚纳克级别的输入检测癌症异常。将 LABS 应用于 100 个患者样本，揭示了癌症特异性模式、拷贝数改变，并通过识别组织起源和免疫细胞组成提高了癌症检测的准确性。
