{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T04:12:59Z","timestamp":1771560779172,"version":"3.50.1"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sunway Medical Centre","award":["SRC\/F\/18\/007"],"award-info":[{"award-number":["SRC\/F\/18\/007"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>This is a pilot proof-of-concept study to evaluate the utility of a custom 15-gene circulating tumor DNA (ctDNA) panel as a potential companion molecular next-generation sequencing (NGS) assay for identifying somatic single nucleotide variants and indels in non-small-cell lung cancer (NSCLC) patients. The custom panel covers the hotspot mutations in <jats:italic>EGFR<\/jats:italic>, <jats:italic>KRAS<\/jats:italic>, <jats:italic>NRAS<\/jats:italic>, <jats:italic>BRAF<\/jats:italic>, <jats:italic>PIK3CA<\/jats:italic>, <jats:italic>ERBB2<\/jats:italic>, <jats:italic>MET<\/jats:italic>, <jats:italic>KIT<\/jats:italic>, <jats:italic>PDGFRA<\/jats:italic>, <jats:italic>ALK<\/jats:italic>, <jats:italic>ROS1<\/jats:italic>, <jats:italic>RET<\/jats:italic>, <jats:italic>NTRK1<\/jats:italic>, <jats:italic>NTRK2<\/jats:italic> and <jats:italic>NTRK3<\/jats:italic> genes which serve as biomarkers for guiding treatment decisions in NSCLC patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Method<\/jats:title>\n<jats:p>The custom 15-gene ctDNA NGS panel was designed using ArcherDX Assay Designer. A total of 20 ng or 50 ng input ctDNA was used to construct the libraries. The analytical performance was evaluated using reference standards at different allellic frequencies (0.1%, 1%, 5% and parental). The clinical performance was evaluated using plasma samples collected from 10 treatment na\u00efve advanced stage III or IV NSCLC patients who were tested for tissue <jats:italic>EGFR<\/jats:italic> mutations. The bioinformatics analysis was performed using the proprietary Archer Analysis Software.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>For the analytical validation, we achieved 100% sensitivity and specificity for the detection of known mutations in the reference standards. The limit of detection was 1% allelic frequency. Clinical validation showed that the clinical sensitivity and specificity of the assay for detecting <jats:italic>EGFR<\/jats:italic> mutation were 83.3% and 100% respectively. In addition, the NGS panel also detected other mutations of uncertain significance in 6 out of 10 patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This preliminary analysis showed that the custom 15-gene ctDNA NGS panel demonstrated good analytical and clinical performances for the <jats:italic>EGFR<\/jats:italic> mutation. Further studies incorporating the validation of other candidate gene mutations are warranted.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0276161","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T17:34:14Z","timestamp":1666114454000},"page":"e0276161","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Analytical and clinical validation of a custom 15-gene next-generation sequencing panel for the evaluation of circulating tumor DNA mutations in patients with advanced non-small-cell lung cancer"],"prefix":"10.1371","volume":"17","author":[{"given":"Yock Ping","family":"Chow","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norziha","family":"Zainul Abidin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken Siong","family":"Kow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lye Mun","family":"Tho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4919-5825","authenticated-orcid":true,"given":"Chieh Lee","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"pone.0276161.ref001","unstructured":"International Agency for Research on Cancer. Malaysia. https:\/\/gco.iarc.fr\/today\/data\/factsheets\/populations\/458-malaysia-fact-sheets.pdf."},{"key":"pone.0276161.ref002","unstructured":"Malaysia National Cancer Registry Report 2012\u20132016. https:\/\/www.moh.gov.my\/moh\/resources\/Penerbitan\/Laporan\/Umum\/2012-2016%20(MNCRR)\/MNCR_2012-2016_FINAL_(PUBLISHED_2019).pdf"},{"issue":"7","key":"pone.0276161.ref003","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.21037\/tlcr-21-52","article-title":"Is there any place for PD-1\/CTLA-4 inhibitors combination in the first-line treatment of advanced NSCLC?-a trial-level meta-analysis in PD-L1 selected subgroups","volume":"10","author":"F Passiglia","year":"2021","journal-title":"Transl Lung Cancer Res"},{"issue":"7","key":"pone.0276161.ref004","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1002\/cam4.3649","article-title":"Integration of comprehensive genomic profiling, tumor mutational burden, and PD-L1 expression to identify novel biomarkers of immunotherapy in non-small cell lung cancer","volume":"10","author":"Y Shi","year":"2021","journal-title":"Cancer Med"},{"issue":"6","key":"pone.0276161.ref005","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s00408-020-00407-5","article-title":"Update 2020: Management of Non-Small Cell Lung Cancer","volume":"198","author":"M Alexander","year":"2020","journal-title":"Lung"},{"issue":"1","key":"pone.0276161.ref006","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13045-020-00881-7","article-title":"Emerging therapeutic agents for advanced non-small cell lung cancer","volume":"13","author":"R Chen","year":"2020","journal-title":"J Hematol Oncol"},{"key":"pone.0276161.ref007","doi-asserted-by":"crossref","first-page":"103119","DOI":"10.1016\/j.critrevonc.2020.103119","article-title":"Beyond EGFR, ALK and ROS1: Current evidence and future perspectives on newly targetable oncogenic drivers in lung adenocarcinoma","volume":"156","author":"G Lamberti","year":"2020","journal-title":"Crit Rev Oncol Hematol"},{"key":"pone.0276161.ref008","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.lungcan.2019.08.005","article-title":"Molecular testing for advanced non-small cell lung cancer in Malaysia: Consensus statement from the College of Pathologists, Academy of Medicine Malaysia, the Malaysian Thoracic Society, and the Malaysian Oncological Society","volume":"136","author":"P Rajadurai","year":"2019","journal-title":"Lung Cancer"},{"issue":"2","key":"pone.0276161.ref009","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1158\/2159-8290.CD-16-1123","article-title":"Targeting ALK: Precision Medicine Takes on Drug Resistance","volume":"7","author":"JJ Lin","year":"2017","journal-title":"Cancer Discov"},{"issue":"7467","key":"pone.0276161.ref010","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nature12625","article-title":"The causes and consequences of genetic heterogeneity in cancer evolution","volume":"501","author":"RA Burrell","year":"2013","journal-title":"Nature"},{"issue":"12","key":"pone.0276161.ref011","doi-asserted-by":"crossref","first-page":"3804","DOI":"10.3390\/cancers12123804","article-title":"Next Generation Sequencing-Based Profiling of Cell Free DNA in Patients with Advanced Non-Small Cell Lung Cancer: Advantages and Pitfalls","volume":"12","author":"R Esposito Abate","year":"2020","journal-title":"Cancers (Basel)"},{"key":"pone.0276161.ref012","first-page":"69","article-title":"Liquid Biopsy in Non-Small Cell Lung Cancer","volume":"3","author":"MA Molina-Vila","year":"2016","journal-title":"Frontiers in medicine"},{"issue":"4","key":"pone.0276161.ref013","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3390\/diagnostics10040215","article-title":"Liquid Biopsy as Novel Tool in Precision Medicine: Origins, Properties, Identification and Clinical Perspective of Cancer\u2019s Biomarkers","volume":"10","author":"D Fern\u00e1ndez-L\u00e1zaro","year":"2020","journal-title":"Diagnostics (Basel)"},{"key":"pone.0276161.ref014","doi-asserted-by":"crossref","first-page":"532403","DOI":"10.3389\/fonc.2020.532403","article-title":"Molecular Profiling-Based Precision Medicine in Cancer: A Review of Current Evidence and Challenges","volume":"10","author":"Q Zhang","year":"2020","journal-title":"Front Oncol"},{"key":"pone.0276161.ref015","doi-asserted-by":"crossref","first-page":"103525","DOI":"10.1016\/j.critrevonc.2021.103525","article-title":"Next generation diagnostic algorithm in non-small cell lung cancer predictive molecular pathology: The KWAY Italian multicenter cost evaluation study","volume":"169","author":"P Pisapia","year":"2022","journal-title":"Crit Rev Oncol Hematol"},{"issue":"1","key":"pone.0276161.ref016","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41598-017-00520-1","article-title":"Circulating Tumor DNA Mutation Profiling by Targeted Next Generation Sequencing Provides Guidance for Personalized Treatments in Multiple Cancer Types","volume":"7","author":"Y Shu","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0276161.ref017","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s12943-018-0875-0","article-title":"Heterogeneous mutation pattern in tumor tissue and circulating tumor DNA warrants parallel NGS panel testing","volume":"17","author":"Q Guo","year":"2018","journal-title":"Mol Cancer"},{"key":"pone.0276161.ref018","first-page":"1","article-title":"Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer","volume":"9","author":"VH Veldore","year":"2018","journal-title":"Lung Cancer (Auckl)"},{"issue":"5","key":"pone.0276161.ref019","doi-asserted-by":"crossref","first-page":"e0232754","DOI":"10.1371\/journal.pone.0232754","article-title":"Liquid biopsy-based tumor profiling for metastatic colorectal cancer patients with ultra-deep targeted sequencing","volume":"15","author":"JK Kang","year":"2020","journal-title":"PLoS One"},{"key":"pone.0276161.ref020","first-page":"4259293","article-title":"Concordance of Genomic Alterations between Circulating Tumor DNA and Matched Tumor Tissue in Chinese Patients with Breast Cancer","author":"B Xu","year":"2020","journal-title":"J Oncol"},{"issue":"9","key":"pone.0276161.ref021","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1373\/clinchem.2015.241414","article-title":"Diagnostic Accuracy of Noninvasive Genotyping of EGFR in Lung Cancer Patients by Deep Sequencing of Plasma Cell-Free DNA","volume":"61","author":"J Uchida","year":"2015","journal-title":"Clin Chem"},{"issue":"7","key":"pone.0276161.ref022","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1158\/1535-7163.MCT-17-0061","article-title":"Concordance of Genomic Alterations by Next-Generation Sequencing in Tumor Tissue versus Circulating Tumor DNA in Breast Cancer","volume":"16","author":"YK Chae","year":"2017","journal-title":"Mol Cancer Ther"},{"issue":"20","key":"pone.0276161.ref023","doi-asserted-by":"crossref","first-page":"33614","DOI":"10.18632\/oncotarget.16833","article-title":"Correlation of genomic alterations assessed by next-generation sequencing (NGS) of tumor tissue DNA and circulating tumor DNA (ctDNA) in metastatic renal cell carcinoma (mRCC): potential clinical implications","volume":"8","author":"AW Hahn","year":"2017","journal-title":"Oncotarget"},{"issue":"7511","key":"pone.0276161.ref024","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nature13385","article-title":"Comprehensive molecular profiling of lung adenocarcinoma","volume":"511","author":"Cancer Genome Atlas Research Network","year":"2014","journal-title":"Nature"},{"issue":"20","key":"pone.0276161.ref025","doi-asserted-by":"crossref","first-page":"7360","DOI":"10.1002\/cam4.4178","article-title":"Driver gene alterations profiling of Chinese non-small cell lung cancer and the effects of co-occurring alterations on immunotherapy","volume":"10","author":"S Sun","year":"2021","journal-title":"Cancer Med"},{"issue":"1","key":"pone.0276161.ref026","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.1038\/s41598-020-59744-3","article-title":"Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population","volume":"10","author":"AH Dang","year":"2020","journal-title":"Sci Rep"},{"key":"pone.0276161.ref027","article-title":"Targeting non-small cell lung cancer: driver mutation beyond epidermal growth factor mutation and anaplastic lymphoma kinase fusion","volume":"12","author":"QS Chu","year":"2020","journal-title":"Ther Adv Med Oncol"},{"issue":"2","key":"pone.0276161.ref028","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/bib\/bbs017","article-title":"Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration","volume":"14","author":"H Thorvaldsd\u00f3ttir","year":"2013","journal-title":"Brief Bioinform"},{"issue":"10","key":"pone.0276161.ref029","doi-asserted-by":"crossref","first-page":"e0140712","DOI":"10.1371\/journal.pone.0140712","article-title":"Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative, Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA","volume":"10","author":"RB Lanman","year":"2015","journal-title":"PLoS One"},{"issue":"10","key":"pone.0276161.ref030","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1515\/cclm-2019-0142","article-title":"Analytical and clinical validation of a novel amplicon-based NGS assay for the evaluation of circulating tumor DNA in metastatic colorectal cancer patients","volume":"57","author":"B Wang","year":"2019","journal-title":"Clin Chem Lab Med"},{"issue":"8","key":"pone.0276161.ref031","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.3390\/app10082895","article-title":"Performance of the OncomineTM Lung cfDNA Assay for Liquid Biopsy by NGS of NSCLC Patients in Routine Laboratory Practice","volume":"10","author":"G De Luca","year":"2020","journal-title":"Appl. Sci"},{"issue":"1","key":"pone.0276161.ref032","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1186\/s12864-015-1806-8","article-title":"Reducing amplification artifacts in high multiplex amplicon sequencing by using molecular barcodes","volume":"16","author":"Q Peng","year":"2015","journal-title":"BMC Genomics"},{"issue":"1","key":"pone.0276161.ref033","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1186\/s12864-019-5583-7","article-title":"Performance evaluation of commercial library construction kits for PCR-based targeted sequencing using a unique molecular identifier","volume":"20","author":"J Chung","year":"2019","journal-title":"BMC Genomics"},{"issue":"9","key":"pone.0276161.ref034","first-page":"2892","article-title":"EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII)","volume":"5","author":"A Midha","year":"2015","journal-title":"Am J Cancer Res"},{"issue":"1","key":"pone.0276161.ref035","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1038\/s41598-019-39965-x","article-title":"Mutational profile of Brazilian lung adenocarcinoma unveils association of EGFR mutations with high Asian ancestry and independent prognostic role of KRAS mutations","volume":"9","author":"LF Leal","year":"2019","journal-title":"Sci Rep"},{"issue":"3","key":"pone.0276161.ref036","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.jtho.2019.10.021","article-title":"Lung Cancer in Malaysia","volume":"15","author":"P Rajadurai","year":"2020","journal-title":"J Thorac Oncol"},{"key":"pone.0276161.ref037","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.lungcan.2018.01.005","article-title":"Real world treatment and outcomes in EGFR mutation-positive non-small cell lung cancer: Long-term follow-up of a large patient cohort","volume":"117","author":"I Okamoto","year":"2018","journal-title":"Lung Cancer"},{"issue":"12","key":"pone.0276161.ref038","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1093\/annonc\/mdz415","article-title":"First-line EGFR TKI therapy in non-small-cell lung cancer: looking back before leaping forward","volume":"30","author":"C Kim","year":"2019","journal-title":"Ann Oncol"},{"issue":"10","key":"pone.0276161.ref039","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1111\/1759-7714.13154","article-title":"Plasma next generation sequencing and droplet digital PCR-based detection of epidermal growth factor receptor (EGFR) mutations in patients with advanced lung cancer treated with subsequent-line osimertinib","volume":"10","author":"PN Ding","year":"2019","journal-title":"Thorac Cancer"},{"key":"pone.0276161.ref040","doi-asserted-by":"crossref","first-page":"104515","DOI":"10.1016\/j.yexmp.2020.104515","article-title":"Clinical implementation of plasma EGFR T790M testing using droplet digital PCR in TKI-resistant NSCLC patients","volume":"116","author":"DLH Chan","year":"2020","journal-title":"Exp Mol Pathol"},{"key":"pone.0276161.ref041","doi-asserted-by":"crossref","first-page":"290","DOI":"10.3389\/fonc.2020.00290","article-title":"Diagnostic Accuracy of Droplet Digital PCR and Amplification Refractory Mutation System PCR for Detecting EGFR Mutation in Cell-Free DNA of Lung Cancer: A Meta-Analysis","volume":"10","author":"C Li","year":"2020","journal-title":"Front Oncol"},{"issue":"9","key":"pone.0276161.ref042","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1038\/nm.1789","article-title":"Circulating mutant DNA to assess tumor dynamics","volume":"14","author":"F Diehl","year":"2008","journal-title":"Nat Med"},{"key":"pone.0276161.ref043","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s43018-020-0043-5","article-title":"Circulating tumor DNA and liquid biopsy in oncology","volume":"1","author":"DW Cescon","year":"2020","journal-title":"Nat Cancer"},{"issue":"25","key":"pone.0276161.ref044","doi-asserted-by":"crossref","first-page":"5900","DOI":"10.1200\/JCO.2005.02.857","article-title":"Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib","volume":"23","author":"DA Eberhard","year":"2005","journal-title":"J Clin Oncol"},{"issue":"31","key":"pone.0276161.ref045","doi-asserted-by":"crossref","first-page":"E2127","DOI":"10.1073\/pnas.1203530109","article-title":"Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1","volume":"109","author":"K Ohashi","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"pone.0276161.ref046","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1158\/2159-8290.CD-12-0108","article-title":"HER2 amplification: a potential mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers that lack the second-site EGFRT790M mutation","volume":"2","author":"K Takezawa","year":"2012","journal-title":"Cancer Discov"},{"issue":"11","key":"pone.0276161.ref047","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1038\/bjc.2014.401","article-title":"Coexistence of KRAS mutation with mutant but not wild-type EGFR predicts response to tyrosine-kinase inhibitors in human lung cancer","volume":"111","author":"A Choughule","year":"2014","journal-title":"Br J Cancer"},{"issue":"11","key":"pone.0276161.ref048","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1038\/bjc.2014.210","article-title":"Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung cancer: a comprehensive mutation profiling from 5125 Chinese cohorts","volume":"110","author":"S Li","year":"2014","journal-title":"Br J Cancer"},{"issue":"8","key":"pone.0276161.ref049","doi-asserted-by":"crossref","first-page":"13611","DOI":"10.18632\/oncotarget.6957","article-title":"Contribution of KRAS mutations and c.2369C > T (p.T790M) EGFR to acquired resistance to EGFR-TKIs in EGFR mutant NSCLC: a study on circulating tumor DNA","volume":"8","author":"M Del Re","year":"2017","journal-title":"Oncotarget"},{"issue":"3","key":"pone.0276161.ref050","doi-asserted-by":"crossref","first-page":"197","DOI":"10.4132\/jptm.2016.03.09","article-title":"Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases","volume":"50","author":"T Lee","year":"2016","journal-title":"J Pathol Transl Med"},{"key":"pone.0276161.ref051","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.lungcan.2017.08.018","article-title":"De novo ERBB2 amplification causing intrinsic resistance to erlotinib in EGFR-L858R mutated TKI-na\u00efve lung 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