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We investigated the characteristics of complex\n                      <jats:italic>ALK<\/jats:italic>\n                      rearrangements in non-small cell lung cancers using multiple molecular tests.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Samples of non-small cell lung cancer patients were analyzed by targeted-capture DNA-based NGS with probes tilling the selected intronic regions of fusion partner genes, RNA-based NGS, RT-PCR, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In a large cohort of 6576 non-small cell lung cancer patients, 343 (5.2%) cases harboring\n                      <jats:italic>ALK<\/jats:italic>\n                      rearrangements were identified. Fourteen cases with complex\n                      <jats:italic>ALK<\/jats:italic>\n                      rearrangements were identified by DNA-based NGS and classified into three types by integrating various genomic features, including intergenic (n\u2009=\u20093), intragenic (n\u2009=\u20095) and \u201cbridge joint\u201d rearrangements (n\u2009=\u20096). All thirteen cases with sufficient samples actually expressed canonical\n                      <jats:italic>EML4-ALK<\/jats:italic>\n                      fusion transcripts confirmed by RNA-based NGS. Besides, positive ALK IHC was detected in 13 of 13 cases, and 9 of 11 cases were positive in FISH testing. Patients with complex\n                      <jats:italic>ALK<\/jats:italic>\n                      rearrangements who received\n                      <jats:italic>ALK<\/jats:italic>\n                      inhibitors treatment (n\u2009=\u20096), showed no difference in progression-free survival (PFS) compared with patients with canonical\n                      <jats:italic>ALK<\/jats:italic>\n                      fusions n\u2009=\u200936,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.9291).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study firstly reveals the molecular characteristics and clinical outcomes of complex\n                      <jats:italic>ALK<\/jats:italic>\n                      rearrangements in NSCLC, sensitive to ALK inhibitors treatment, and highlights the importance of utilizing probes tilling the selected intronic regions of fusion partner genes in DNA-based NGS for accurate fusion detection. RNA and protein level assay may be critical in validating the function of complex\n                      <jats:italic>ALK<\/jats:italic>\n                      rearrangements in clinical practice for optimal treatment decision.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-021-02982-4","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T07:02:54Z","timestamp":1626418974000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Molecular characteristics and clinical outcomes of complex ALK rearrangements identified by next-generation sequencing in non-small cell lung cancers"],"prefix":"10.1186","volume":"19","author":[{"given":"Peiyi","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enjie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxing","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6306-726X","authenticated-orcid":false,"given":"Guozhong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"key":"2982_CR1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1158\/2159-8290.CD-16-1123","volume":"7","author":"JJ Lin","year":"2017","unstructured":"Lin JJ, Riely GJ, Shaw AT. 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