Sensitive tumour detection and classification using plasma cell-free DNA methylomes
Sensitive tumour detection and classification using plasma cell-free DNA methylomes
复制标题
DOI：
10.1038/s41586-018-0703-0
复制
发表时间：
2018-11-22
期刊：
影响因子：
64.8
通讯作者：
De Carvalho, Daniel D.
中科院分区：
文献类型：
--
作者：
Shen, Shu Yi;Singhania, Rajat;De Carvalho, Daniel D.
使用液体活检进行癌症检测和管理正在迅速获得重视（1）。目前用于检测循环肿瘤DNA的方法涉及使用无细胞DNA对体细胞突变进行测序，但是鉴于复发突变的数量有限，这些方法在患有早期癌症的患者中的灵敏度可能较低（2-5）。相比之下，大规模的表观遗传改变-在这里，我们开发了一种灵敏的，基于免疫沉淀的方案来分析少量循环无细胞DNA的甲基化组，并证明了检测大规模DNA甲基化变化的能力，这些变化富含肿瘤特异性模式。我们还在来自几种肿瘤类型的大量血浆样本中展示了癌症检测和分类的稳健性能。这项工作为基于血浆游离DNA甲基化模式建立用于早期癌症的微创检测、拦截和分类的生物标志物奠定了基础。
The use of liquid biopsies for cancer detection and management is rapidly gaining prominence(1). Current methods for the detection of circulating tumour DNA involve sequencing somatic mutations using cell-free DNA, but the sensitivity of these methods may be low among patients with early-stage cancer given the limited number of recurrent mutations(2-5). By contrast, large-scale epigenetic alterations-which are tissue-and cancer-type specific-are not similarly constrained(6) and therefore potentially have greater ability to detect and classify cancers in patients with early-stage disease. Here we develop a sensitive, immunoprecipitation-based protocol to analyse the methylome of small quantities of circulating cellfree DNA, and demonstrate the ability to detect large-scale DNA methylation changes that are enriched for tumour-specific patterns. We also demonstrate robust performance in cancer detection and classification across an extensive collection of plasma samples from several tumour types. This work sets the stage to establish biomarkers for the minimally invasive detection, interception and classification of early-stage cancers based on plasma cell-free DNA methylation patterns.