文章：

早期癌症检测中游离DNA的基因组和片段组学研究

Genomic and fragmentomic landscapes of cell-free DNA for early cancer detection

原文发布日期：2025-03-04

DOI: 10.1038/s41568-025-00795-x

类型: Review Article

开放获取: 否

英文摘要：

Genomic analyses of cell-free DNA (cfDNA) in plasma are enabling noninvasive blood-based biomarker approaches to cancer detection and disease monitoring. Current approaches for identification of circulating tumour DNA typically use targeted tumour-specific mutations or methylation analyses. An emerging approach is based on the recognition of altered genome-wide cfDNA fragmentation in patients with cancer. Recent studies have revealed a multitude of characteristics that can affect the compendium of cfDNA fragments across the genome, collectively called the ‘cfDNA fragmentome’. These changes result from genomic, epigenomic, transcriptomic and chromatin states of an individual and affect the size, position, coverage, mutation, structural and methylation characteristics of cfDNA. Identifying and monitoring these changes has the potential to improve early detection of cancer, especially using highly sensitive multi-feature machine learning approaches that would be amenable to broad use in populations at increased risk. This Review highlights the rapidly evolving field of genome-wide analyses of cfDNA characteristics, their comparison to existing cfDNA methods, and recent related innovations at the intersection of large-scale sequencing and artificial intelligence. As the breadth of clinical applications of cfDNA fragmentome methods have enormous public health implications for cancer screening and personalized approaches for clinical management of patients with cancer, we outline the challenges and opportunities ahead.

摘要翻译： 

血浆中无细胞DNA（cfDNA）的基因组分析正推动基于血液的非侵入性生物标志物方法在癌症检测与疾病监测中的应用。目前识别循环肿瘤DNA的方法通常采用靶向肿瘤特异性突变或甲基化分析。一种新兴方法基于对癌症患者全基因组cfDNA片段化改变的识别。近期研究揭示了多种影响全基因组cfDNA片段组谱的特征，这些特征被统称为“cfDNA片段组”。这些变化源于个体的基因组、表观基因组、转录组和染色质状态，并影响cfDNA的大小、位置、覆盖度、突变、结构和甲基化特征。识别和监测这些变化有望改善癌症早期检测，特别是采用适用于高危人群广泛使用的、高灵敏度的多特征机器学习方法。本综述重点探讨cfDNA特征全基因组分析这一快速发展领域，将其与现有cfDNA方法进行比较，并介绍大规模测序与人工智能交叉领域的最新创新。鉴于cfDNA片段组方法的临床应用广度对癌症筛查和癌症患者临床管理的个性化方法具有重大公共卫生意义，我们展望了未来面临的挑战与机遇。

原文链接：

Genomic and fragmentomic landscapes of cell-free DNA for early cancer detection