title: A targeted next-generation sequencing method for identifying clinically relevant mutation profiles in lung adenocarcinoma.
abstract: Molecular profiling of lung cancer has become essential for prediction of an individual's response to targeted therapies. Next-generation sequencing (NGS) is a promising technique for routine diagnostics, but has not been sufficiently evaluated in terms of feasibility, reliability, cost and capacity with routine diagnostic formalin-fixed, paraffin-embedded (FFPE) materials. Here, we report the validation and application of a test based on Ion Proton technology for the rapid characterisation of single nucleotide variations (SNVs), short insertions and deletions (InDels), copy number variations (CNVs), and gene rearrangements in 145 genes with FFPE clinical specimens. The validation study, using 61 previously profiled clinical tumour samples, showed a concordance rate of 100% between results obtained by NGS and conventional test platforms. Analysis of tumour cell lines indicated reliable mutation detection in samples with 5% tumour content. Furthermore, application of the panel to 58 clinical cases, identified at least one actionable mutation in 43 cases, 1.4 times the number of actionable alterations detected by current diagnostic tests. We demonstrated that targeted NGS is a cost-effective and rapid platform to detect multiple mutations simultaneously in various genes with high reproducibility and sensitivity.
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.|Department of Biology, University of Copenhagen, Copenhagen, DK-2200, Denmark.|BGI-Guangzhou, Guangzhou Key Laboratory of Cancer Trans-Omics Research, Guangzhou, 510006, China.
authors.forename: Di
authors.initials: D
authors.lastname: Shao
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.|Centre of Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.|The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Lin
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Jilong
authors.initials: J
authors.lastname: Liu
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wan
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Zu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Shaomin
authors.initials: S
authors.lastname: Cheng
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Lingna
authors.initials: L
authors.lastname: Fei
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Rongqing
authors.initials: R
authors.lastname: Deng
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Gu
authors.affiliation: The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Liang
authors.affiliation: The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, DK-2200, Denmark.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: BGI-Shenzhen, Shenzhen, 518083, China.|Department of Biology, University of Copenhagen, Copenhagen, DK-2200, Denmark.|BGI-Guangzhou, Guangzhou Key Laboratory of Cancer Trans-Omics Research, Guangzhou, 510006, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Ye
authors.affiliation: The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
authors.forename: Jianxing
authors.initials: J
authors.lastname: He
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015203:Reproducibility of Results