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

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 usin...

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Autores principales: Peng, Hao, Lu, Lan, Zhou, Zisong, Liu, Jian, Zhang, Dadong, Nan, Kejun, Zhao, Xiaochen, Li, Fugen, Tian, Lei, Dong, Hua, Yao, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895974/
https://www.ncbi.nlm.nih.gov/pubmed/31739500
http://dx.doi.org/10.3390/genes10110926
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author Peng, Hao
Lu, Lan
Zhou, Zisong
Liu, Jian
Zhang, Dadong
Nan, Kejun
Zhao, Xiaochen
Li, Fugen
Tian, Lei
Dong, Hua
Yao, Yu
author_facet Peng, Hao
Lu, Lan
Zhou, Zisong
Liu, Jian
Zhang, Dadong
Nan, Kejun
Zhao, Xiaochen
Li, Fugen
Tian, Lei
Dong, Hua
Yao, Yu
author_sort Peng, Hao
collection PubMed
description 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.
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spelling pubmed-68959742019-12-24 CNV Detection from Circulating Tumor DNA in Late Stage Non-Small Cell Lung Cancer Patients Peng, Hao Lu, Lan Zhou, Zisong Liu, Jian Zhang, Dadong Nan, Kejun Zhao, Xiaochen Li, Fugen Tian, Lei Dong, Hua Yao, Yu Genes (Basel) Article 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. MDPI 2019-11-14 /pmc/articles/PMC6895974/ /pubmed/31739500 http://dx.doi.org/10.3390/genes10110926 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Peng, Hao
Lu, Lan
Zhou, Zisong
Liu, Jian
Zhang, Dadong
Nan, Kejun
Zhao, Xiaochen
Li, Fugen
Tian, Lei
Dong, Hua
Yao, Yu
CNV Detection from Circulating Tumor DNA in Late Stage Non-Small Cell Lung Cancer Patients
title CNV Detection from Circulating Tumor DNA in Late Stage Non-Small Cell Lung Cancer Patients
title_full CNV Detection from Circulating Tumor DNA in Late Stage Non-Small Cell Lung Cancer Patients
title_fullStr CNV Detection from Circulating Tumor DNA in Late Stage Non-Small Cell Lung Cancer Patients
title_full_unstemmed CNV Detection from Circulating Tumor DNA in Late Stage Non-Small Cell Lung Cancer Patients
title_short CNV Detection from Circulating Tumor DNA in Late Stage Non-Small Cell Lung Cancer Patients
title_sort cnv detection from circulating tumor dna in late stage non-small cell lung cancer patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895974/
https://www.ncbi.nlm.nih.gov/pubmed/31739500
http://dx.doi.org/10.3390/genes10110926
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