当前位置:科学网首页 > 小柯机器人 >详情
新方法可对癌症实现超灵敏监测
作者:小柯机器人 发布时间:2020/6/2 20:19:07

美国纽约基因组中心Dan A. Landau研究组的研究通过整合无细胞全基因组DNA突变实现了对癌症的超灵敏监测。该研究于2020年6月1日发表于《自然—医学》杂志。

在肿瘤学的许多领域,缺乏跟踪低负荷疾病的灵敏工具。尽管无细胞DNA(cfDNA)有望助力于癌症突变检测,但研究发现低肿瘤分数(TF)和有限数量的DNA片段同时限制了低负荷疾病的监测。研究人员认为测序广度可以取代测序深度,从而克服cfDNA丰度的障碍。

cfDNA的全基因组测序(WGS)利用在恶性实体肿瘤中观察到的数千个体细胞突变的累积信号实现了超灵敏检测,TF检测的灵敏度低至10-5。WGS方法可实现动态肿瘤负荷跟踪和术后伴有不良反应残留疾病的检测。因此,该研究提出了利用全基因组突变整合监测cfDNA癌症的正交网络,从而能够进行超灵敏检测,克服cfDNA丰度的局限性并在低发病风险的肿瘤护理中增强治疗效果。

附:英文原文

Title: Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring

Author: Asaf Zviran, Rafael C. Schulman, Minita Shah, Steven T. K. Hill, Sunil Deochand, Cole C. Khamnei, Dillon Maloney, Kristofer Patel, Will Liao, Adam J. Widman, Phillip Wong, Margaret K. Callahan, Gavin Ha, Sarah Reed, Denisse Rotem, Dennie Frederick, Tatyana Sharova, Benchun Miao, Tommy Kim, Greg Gydush, Justin Rhoades, Kevin Y. Huang, Nathaniel D. Omans, Patrick O. Bolan, Andrew H. Lipsky, Chelston Ang, Murtaza Malbari, Catherine F. Spinelli, Selena Kazancioglu, Alexi M. Runnels, Samantha Fennessey, Christian Stolte, Federico Gaiti, Giorgio G. Inghirami, Viktor Adalsteinsson, Brian Houck-Loomis, Jennifer Ishii, Jedd D. Wolchok, Genevieve Boland, Nicolas Robine, Nasser K. Altorki, Dan A. Landau

Issue&Volume: 2020-06-01

Abstract: In many areas of oncology, we lack sensitive tools to track low-burden disease. Although cell-free DNA (cfDNA) shows promise in detecting cancer mutations, we found that the combination of low tumor fraction (TF) and limited number of DNA fragments restricts low-disease-burden monitoring through the prevailing deep targeted sequencing paradigm. We reasoned that breadth may supplant depth of sequencing to overcome the barrier of cfDNA abundance. Whole-genome sequencing (WGS) of cfDNA allowed ultra-sensitive detection, capitalizing on the cumulative signal of thousands of somatic mutations observed in solid malignancies, with TF detection sensitivity as low as 105. The WGS approach enabled dynamic tumor burden tracking and postoperative residual disease detection, associated with adverse outcome. Thus, we present an orthogonal framework for cfDNA cancer monitoring via genome-wide mutational integration, enabling ultra-sensitive detection, overcoming the limitation of cfDNA abundance and empowering treatment optimization in low-disease-burden oncology care.

DOI: 10.1038/s41591-020-0915-3

Source: https://www.nature.com/articles/s41591-020-0915-3

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex