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Open AccessArticle

CNV Detection from Circulating Tumor DNA in Late Stage Non-Small Cell Lung Cancer Patients

by Hao Peng 1,†, Lan Lu 2,†, Zisong Zhou 3,†, Jian Liu 4, Dadong Zhang 5, Kejun Nan 6, Xiaochen Zhao 7, Fugen Li 3, Lei Tian 8,*, Hua Dong 3,* and Yu Yao 6,*
1
Department of Clinical Medicine, Kunming University of Science and Technology, Yunnan 650093, China
2
National Cancer Center, National Clinical Research Center for Cancer, Shenzhen 518116, China
3
The Bioinformatics Department, 3D Medicines Inc., Shanghai 201114, China
4
Department of Clinical Medicine, Guangzhou Medical University, Guangzhou 511436, China
5
The Translational Medicine Department, 3D Medicines Inc., Shanghai 201114, China
6
Department of Medical Oncology, Xi’an Jiaotong University, Shaanxi 710061, China
7
The Medical Department, 3D Medicines Inc., Shanghai 201114, China
8
Department of Thoracic Surgery Clinical Colleage, Chongqing Medical University, Chongqing 400016, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Genes 2019, 10(11), 926; https://doi.org/10.3390/genes10110926
Received: 12 October 2019 / Revised: 8 November 2019 / Accepted: 12 November 2019 / Published: 14 November 2019
While methods for detecting SNVs and indels in circulating tumor DNA (ctDNA) with hybridization capture-based next-generation sequencing (NGS) have been available, copy number variations (CNVs) detection is more challenging. Here, we present a method enabling CNV detection from a 150-gene panel using a very low amount of ctDNA. First, a read depth-based CNV estimation method without a paired blood sample was developed and cfDNA sequencing data from healthy people were used to build a panel of normal (PoN) model. Then, in silico and in vitro simulations were performed to define the limit of detection (LOD) for EGFR, ERBB2, and MET. Compared to the WES results of the 48 samples, the concordance rate for EGFR, ERBB2, and MET CNVs was 78%, 89.6%, and 92.4%, respectively. In another cohort profiled with the 150-gene panel from 5980 lung cancer ctDNA samples, we detected the three genes’ amplification with comparable population frequency with other cohorts. One lung adenocarcinoma patient with MET amplification detected by our method reached partial response to crizotinib. These findings show that our ctDNA CNV detection pipeline can detect CNVs with high specificity and concordance, which enables CNV calling in a non-invasive way for cancer patients when tissues are not available. View Full-Text
Keywords: copy number variations; targeted sequencing; circulating tumor DNA; non-small cell lung cancer copy number variations; targeted sequencing; circulating tumor DNA; non-small cell lung cancer
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Peng, H.; Lu, L.; Zhou, Z.; Liu, J.; Zhang, D.; Nan, K.; Zhao, X.; Li, F.; Tian, L.; Dong, H.; Yao, Y. CNV Detection from Circulating Tumor DNA in Late Stage Non-Small Cell Lung Cancer Patients. Genes 2019, 10, 926.

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