美国约翰霍普金斯大学医学院Victor E. Velculescu团队对癌症患者全基因组无细胞DNA片段进行了分析，该研究成果发表在2019年6月出版的《自然》杂志上。

该课题组开发了一种方法来评估基因组中无细胞DNA的碎裂谱，并发现健康个体的特征反映了白细胞的核小体模式，而癌症患者则改变了片段模式。研究人员采用该方法分析了236例乳腺癌、结直肠癌、肺癌、卵巢癌、胰腺癌、胃癌或胆管癌患者和245例健康人的碎片特征。结合了全基因组片段特征的机器学习模型在7种癌症类型中的检测灵敏度从57%到99%以上，特异性为98%，总曲线下面积为0.94。在75%的病例中，碎裂谱可将癌症起源组织鉴定到有限几个位点。将此方法与基于突变的无细胞DNA分析相结合，检测出91%的癌症患者。这些分析结果强调了无细胞DNA的重要特性，并为筛选、早期检测和监测人类癌症提供了一种原理验证方法。

研究人员表示，血液中的无细胞DNA为癌症患者提供了非侵入性的诊断途径。然而目前对无细胞DNA的起源和分子特点的特征知之甚少。

附：英文原文

Title: Genome-wide cell-free DNA fragmentation in patients with cancer

Author: Stephen Cristiano, Alessandro Leal, Jillian Phallen, Jacob Fiksel, Vilmos Adleff, Daniel C. Bruhm, Sarah strup Jensen, Jamie E. Medina, Carolyn Hruban, James R. White, Doreen N. Palsgrove, Noushin Niknafs, Valsamo Anagnostou, Patrick Forde, Jarushka Naidoo, Kristen Marrone, Julie Brahmer, Brian D. Woodward, Hatim Husain, Karlijn L. van Rooijen, Mai-Britt Worm rntoft, Anders Husted Madsen, Cornelis J. H. van de Velde, Marcel Verheij, Annemieke Cats, Cornelis J. A. Punt, Geraldine R. Vink, Nicole C. T. van Grieken, Miriam Koopman, Remond J. A. Fijneman, Julia S. Johansen, Hans Jrgen Nielsen, Gerrit A. Meijer, Claus Lindbjerg Andersen, Robert B. Scharpf, Victor E. Velculescu

Issue&Volume: Volume 570 Issue 7761, 20 June 2019

Abstract: Cell-free DNA in the blood provides a non-invasive diagnostic avenue for patients with cancer1. However, characteristics of the origins and molecular features of cell-free DNA are poorly understood. Here we developed an approach to evaluate fragmentation patterns of cell-free DNA across the genome, and found that profiles of healthy individuals reflected nucleosomal patterns of white blood cells, whereas patients with cancer had altered fragmentation profiles. We used this method to analyse the fragmentation profiles of 236 patients with breast, colorectal, lung, ovarian, pancreatic, gastric or bile duct cancer and 245 healthy individuals. A machine learning model that incorporated genome-wide fragmentation features had sensitivities of detection ranging from 57% to more than 99% among the seven cancer types at 98% specificity, with an overall area under the curve value of 0.94. Fragmentation profiles could be used to identify the tissue of origin of the cancers to a limited number of sites in 75% of cases. Combining our approach with mutation-based cell-free DNA analyses detected 91% of patients with cancer. The results of these analyses highlight important properties of cell-free DNA and provide a proof-of-principle approach for the screening, early detection and monitoring of human cancer.

DOI: 10.1038/s41586-019-1272-6

Source:https://www.nature.com/articles/s41586-019-1272-6