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Integrating genomic features for non-invasive early lung cancer detection 期刊论文
NATURE, 2020, 580 (7802) : 245-+
作者:  Wang, Qinyang;  Wang, Yupeng;  Ding, Jingjin;  Wang, Chunhong;  Zhou, Xuehan;  Gao, Wenqing;  Huang, Huanwei;  Shao, Feng;  Liu, Zhibo
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

Circulating tumour DNA in blood is analysed to identify genomic features that distinguish early-stage lung cancer patients from risk-matched controls, and these are integrated into a machine-learning method for blood-based lung cancer screening.


Radiologic screening of high-risk adults reduces lung-cancer-related mortality(1,2)  however, a small minority of eligible individuals undergo such screening in the United States(3,4). The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)(5), a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed '  lung cancer likelihood in plasma'  (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.


  
Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148 期刊论文
NATURE COMMUNICATIONS, 2017, 8
作者:  Fang, Jun;  39;Neill, Maura
收藏  |  浏览/下载:0/0  |  提交时间:2019/11/27
Constituents of Household Air Pollution and Risk of Lung Cancer among Never-Smoking Women in Xuanwei and Fuyuan, China 期刊论文
ENVIRONMENTAL HEALTH PERSPECTIVES, 2019, 127 (9)
作者:  Vermeulen, Roel;  Downward, George S.;  Zhang, Jinming;  Hu, Wei;  Portengen, Lutzen;  Bassig, Bryan A.;  Hammond, S. Katharine;  Wong, Jason Y. Y.;  Li, Jihua;  Reiss, Boris;  He, Jun;  Tian, Linwei;  Yang, Kaiyun;  Seow, Wei Jie;  Xu, Jun;  Anderson, Kim;  Ji, Bu-Tian;  Silverman, Debra;  Chanock, Stephen;  Huang, Yunchao;  Rothman, Nathaniel;  Lan, Qing
收藏  |  浏览/下载:12/0  |  提交时间:2019/11/27
Cleaner fuels for ships provide public health benefits with climate tradeoffs 期刊论文
NATURE COMMUNICATIONS, 2018, 9
作者:  Sofiev, Mikhail;  Winebrake, James J.;  Johansson, Lasse;  Carr, Edward W.;  Prank, Marje;  Soares, Joana;  Vira, Julius;  Kouznetsov, Rostislav;  Jalkanen, Jukka-Pekka;  Corbett, James J.
收藏  |  浏览/下载:9/0  |  提交时间:2019/11/27
Variability of polycyclic aromatic hydrocarbons and their oxidative derivatives in wintertime Beijing, China 期刊论文
ATMOSPHERIC CHEMISTRY AND PHYSICS, 2019, 19 (13) : 8741-8758
作者:  Elzein, Atallah;  Dunmore, Rachel E.;  Ward, Martyn W.;  Hamilton, Jacqueline F.;  Lewis, Alastair C.
收藏  |  浏览/下载:6/0  |  提交时间:2019/11/27
Mortality Risk and Fine Particulate Air Pollution in a Large, Representative Cohort of US Adults 期刊论文
ENVIRONMENTAL HEALTH PERSPECTIVES, 2019, 127 (7)
作者:  Pope, C. Arden, III;  Lefler, Jacob S.;  Ezzati, Majid;  Higbee, Joshua D.;  Marshall, Julian U.;  Kim, Sun-Young;  Bechle, Matthew;  Gilliat, Kurtis S.;  Vernon, Spencer E.;  Robinson, Allen L.;  Burnett, Richard T.
收藏  |  浏览/下载:7/0  |  提交时间:2019/11/27
RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues 期刊论文
SCIENCE, 2019, 364 (6444) : 970-+
作者:  Yizhak, Keren;  Aguet, Francois;  Kim, Jaegil;  Hess, JulianM.;  Kubler, Kirsten;  Grimsby, Jonna;  Frazer, Ruslana;  Zhang, Hailei;  Haradhvala, Nicholas J.;  Rosebrock, Daniel;  Livitz, Dimitri;  Li, Xiao;  Arich-Landkof, Eila;  Shoresh, Noam;  Stewart, Chip;  Segre, Ayellet V.;  Branton, Philip A.;  Polak, Paz;  Ardlie, Kristin G.;  Getz, Gad
收藏  |  浏览/下载:23/0  |  提交时间:2019/11/27
Health Effects of Household Solid Fuel Use: Findings from 11 Countries within the Prospective Urban and Rural Epidemiology Study 期刊论文
ENVIRONMENTAL HEALTH PERSPECTIVES, 2019, 127 (5)
作者:  Hystad, Perry;  Duong, MyLinh;  Brauer, Michael;  Larkin, Andrew;  Arku, Raphael;  Kurmi, Om P.;  Fan, Wen Qi;  Avezum, Alvaro;  Azam, Igbal;  Chifamba, Jephat;  Dans, Antonio;  du Plessis, Johan L.;  Gupta, Rajeev;  Kumar, Rajesh;  Lanas, Fernando;  Liu, Zhiguang;  Lu, Yin;  Lopez-Jaramillo, Patricio;  Mony, Prem;  Mohan, Viswanathan;  Mohan, Deepa;  Nair, Sanjeev;  Puoane, Thandi;  Rahman, Omar;  Lap, Ah Tse;  Wang, Yanga;  Wei, Li;  Yeates, Karen;  Rangarajan, Sumathy;  Teo, Koon;  Yusuf, Salim
收藏  |  浏览/下载:20/0  |  提交时间:2019/11/26
Radon Risk: A Global Estimate of Radon's Contribution to Lung Cancer 期刊论文
ENVIRONMENTAL HEALTH PERSPECTIVES, 2019, 127 (2)
作者:  Seltenrich, Nate
收藏  |  浏览/下载:2/0  |  提交时间:2019/04/09
A meteorological analysis of PM10 episodes at a high altitude city and a low altitude city in central Greece - The impact of wood burning heating devices 期刊论文
ATMOSPHERIC RESEARCH, 2018, 214: 329-337
作者:  Dimitriou, Konstantinos;  Kassomenos, Pavlos
收藏  |  浏览/下载:12/0  |  提交时间:2019/04/09
PM10  Wood burning  Saharan dust  Central Greece  Air pollution  PSCF model