{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T15:14:36Z","timestamp":1774451676409,"version":"3.50.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"vor","delay-in-days":172,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Next-generation sequencing has mostly been used for genotyping cell-free DNA (cfDNA) in plasma. However, this assay has several clinical limitations. We evaluated the clinical utility of a novel polymerase chain reaction\u2013free nanowire (NW)-based plasma cfDNA assay for detecting ALK fusion and mutations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients, Materials, and Methods<\/jats:title>\n                  <jats:p>We consecutively enrolled 99 patients with advanced non-small cell lung cancer undergoing a fluorescence in situ hybridization (FISH) test for ALK fusion; ALK-positive (n = 36). The NW-based assay was performed using 50\u2013100 \u03bcL of plasma collected at pretreatment and every 8\u2009weeks during ALK inhibitor treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>There was high concordance between the NW-based assay and the FISH test for identification of ALK fusion (94.9% with a kappa coefficient value of 0.892, 95% confidence interval [CI], 0.799\u20130.984). There was no difference in the response rate to the first anaplastic lymphoma kinase inhibitor between the ALK-positive patients identified by the NW-based assay and by the FISH test (73.5% vs. 72.2%, p = .931). In the ALK variant analysis, variants 1 and 3 subgroups were detected in 27 (75.0%) and 8 (22.2%) patients, respectively. Among 24 patients treated with crizotinib, variant 3 subgroup was associated with worse median overall survival than variant 1 subgroup (36.5 months; 95% CI, 0.09\u201387.6 vs. 19.8 months; 95% CI, 9.9\u2013not reached, p = .004]. A serial assessment identified that ALK L1196M resistance mutation emerged before radiologic progression during crizotinib treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The newly developed simple NW-based cfDNA assay may be clinically applicable for rapid diagnosis of ALK fusion with its variant forms and early detection of resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Implications for Practice<\/jats:title>\n                  <jats:p>The authors developed a novel one-step polymerase chain reaction\u2013free nanowire (NW)-based plasma cell-free DNA (cfDNA) assay. This study evaluated the clinical utility of this novel method for the diagnosis of EML4-ALK fusion in advanced non-small cell lung cancer (NSCLC). The NW-based assay and FISH test showed high concordance rate in 99 patients with advanced NSCLC. Serial cfDNA assessment demonstrated this method provided early detection of resistance before radiologic progression during crizotinib treatment. Taken together, plasma cfDNA genotyping by the NW-based cfDNA assay may be useful for the rapid diagnosis of ALK fusion, classifying variants, and early detection of resistance.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/onco.13902","type":"journal-article","created":{"date-parts":[[2021,7,17]],"date-time":"2021-07-17T08:47:24Z","timestamp":1626511644000},"page":"e1683-e1692","source":"Crossref","is-referenced-by-count":5,"title":["One-Step Polymerase Chain Reaction-Free Nanowire-Based Plasma Cell-Free DNA Assay to Detect <i>EML4<\/i>-<i>ALK<\/i> Fusion and to Monitor Resistance in Lung Cancer"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0180-189X","authenticated-orcid":false,"given":"Youngjoo","family":"Lee","sequence":"first","affiliation":[{"name":"Center for Lung Cancer, National Cancer Center Korea, Goyang, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngnam","family":"Cho","sequence":"additional","affiliation":[{"name":"Translational Research Branch, National Cancer Center Korea, Goyang, Republic of Korea"},{"name":"Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, Goyang, Republic of Korea"},{"name":"Genopsy Inc., Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Young","family":"Park","sequence":"additional","affiliation":[{"name":"Biostatics Collaboration Team, National Cancer Center Korea, Goyang, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong-Yun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cancer Center Korea, Goyang, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kum Hui","family":"Hwang","sequence":"additional","affiliation":[{"name":"Center for Lung Cancer, National Cancer Center Korea, Goyang, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Youn","family":"Han","sequence":"additional","affiliation":[{"name":"Center for Lung Cancer, National Cancer Center Korea, Goyang, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,8,2]]},"reference":[{"key":"2022012122081326200_onco13902-bib-0001","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nature05945","article-title":"Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer","volume":"448","author":"Soda","year":"2007","journal-title":"Nature"},{"key":"2022012122081326200_onco13902-bib-0002","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1042\/BJ20090387","article-title":"Anaplastic lymphoma kinase: Signalling in development and disease","volume":"420","author":"Palmer","year":"2009","journal-title":"Biochem 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