Sensitive tumour detection and classification using plasma cell-free DNA methylomes,Nature

当前位置： X-MOL 学术 › Nature › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Sensitive tumour detection and classification using plasma cell-free DNA methylomes
Nature ( IF 50.5 ) Pub Date : 2018-11-01 , DOI: 10.1038/s41586-018-0703-0
Shu Yi Shen ₁ , Rajat Singhania ₁ , Gordon Fehringer ₂ , Ankur Chakravarthy ₁ , Michael H A Roehrl _{1,

3,

4} , Dianne Chadwick ₁ , Philip C Zuzarte ₅ , Ayelet Borgida ₂ , Ting Ting Wang _{1,

4} , Tiantian Li ₁ , Olena Kis ₁ , Zhen Zhao ₁ , Anna Spreafico ₁ , Tiago da Silva Medina ₁ , Yadon Wang ₁ , David Roulois _{1,

6} , Ilias Ettayebi _{1,

4} , Zhuo Chen ₁ , Signy Chow ₁ , Tracy Murphy ₁ , Andrea Arruda ₁ , Grainne M O'Kane ₁ , Jessica Liu ₄ , Mark Mansour ₄ , John D McPherson ₇ , Catherine O'Brien ₁ , Natasha Leighl ₁ , Philippe L Bedard ₁ , Neil Fleshner ₁ , Geoffrey Liu _{1,

4,

8} , Mark D Minden ₁ , Steven Gallinger _{9,

10} , Anna Goldenberg ₁₁ , Trevor J Pugh _{1,

4} , Michael M Hoffman _{1,

4,

11} , Scott V Bratman _{1,

4} , Rayjean J Hung _{2,

8} , Daniel D De Carvalho _{1,

4}

Affiliation

Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Genome Technologies, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
UMR_S 1236, Univ Rennes 1, Inserm, Etablissement Français du sang Bretagne, Rennes, France.
Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, Sacramento, CA, USA.
Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
Fred Litwin Centre for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Department of Surgery, Toronto General Hospital, Toronto, Ontario, Canada.
Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.

The use of liquid biopsies for cancer detection and management is rapidly gaining prominence1. 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 mutations2–5. By contrast, large-scale epigenetic alterations—which are tissue- and cancer-type specific—are not similarly constrained6 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 cell-free 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.An immunoprecipitation-based protocol is developed to analyse DNA methylation in small quantities of circulating cell-free DNA, and can detect and classify cancers in plasma samples from several tumour types.

中文翻译：

使用无浆细胞 DNA 甲基化组进行灵敏的肿瘤检测和分类

液体活检在癌症检测和管理中的应用正迅速受到重视1。目前检测循环肿瘤 DNA 的方法包括使用无细胞 DNA 对体细胞突变进行测序，但鉴于复发突变的数量有限，这些方法在早期癌症患者中的敏感性可能较低2-5。相比之下，组织和癌症类型特异性的大规模表观遗传改变不受类似的限制6，因此在早期疾病患者中可能具有更大的检测和分类癌症的能力。在这里，我们开发了一种灵敏的、基于免疫沉淀的协议来分析少量循环无细胞 DNA 的甲基化组，并证明能够检测到针对肿瘤特异性模式丰富的大规模 DNA 甲基化变化。我们还在来自多种肿瘤类型的大量血浆样本中展示了在癌症检测和分类方面的强大性能。这项工作为建立基于无浆细胞 DNA 甲基化模式的早期癌症微创检测、拦截和分类的生物标志物奠定了基础。开发了一种基于免疫沉淀的协议来分析少量循环细胞中的 DNA 甲基化。游离 DNA，并且可以检测和分类来自多种肿瘤类型的血浆样本中的癌症。

更新日期：2018-11-01

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11