{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:12:39Z","timestamp":1747185159076,"version":"3.40.5"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The advent of specific ALK\u2010targeting drugs has radically changed the outcome of patients with <jats:italic>ALK<\/jats:italic> translocated non\u2010small\u2010cell lung cancer (NSCLC). However, emerging resistance to treatment with <jats:italic>ALK<\/jats:italic> inhibitors in these patients remains a major concern. In previous studies, we analysed two <jats:italic>ALK+<\/jats:italic> patient cohorts (<jats:italic>TP53<\/jats:italic> wild\u2010type\/<jats:italic>TP53<\/jats:italic> mutated) in terms of copy number alterations. All patients belonging to the <jats:italic>TP53<\/jats:italic> wild\u2010type group had mainly genetically stable genomes, with one exception showing chromosomal instability and amplifications of several gene loci, including <jats:italic>TERT<\/jats:italic>. Here, we aimed to determine the prevalence of <jats:italic>TERT<\/jats:italic> amplifications in these <jats:italic>ALK+<\/jats:italic> lung cancer patients by analysing an independent cohort of 109 <jats:italic>ALK<\/jats:italic> translocated cases. We further analysed the copy numbers of numerous cancer\u2010relevant genes and other genetic aberrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>The prevalence of <jats:italic>TERT<\/jats:italic> amplifications was determined by means of FISH analyses. Copy numbers of 87 cancer\u2010relevant genes were determined by NanoString nCounter<jats:sup>\u00ae<\/jats:sup> technology, FoundationOne<jats:sup>\u00ae<\/jats:sup> and lung\u2010specific NGS panels in some of these <jats:italic>TERT<\/jats:italic>\u2010amplified samples, and clinical data on patients with <jats:italic>TERT<\/jats:italic>\u2010amplified tumours were collected. Our data revealed that five (4.6%) of all 109 analysed <jats:italic>ALK+<\/jats:italic> patients harboured amplification of <jats:italic>TERT<\/jats:italic> and that these patients had genetically unstable genomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our preliminary study shows that <jats:italic>ALK<\/jats:italic>+ adenocarcinomas should be evaluated in the context of their genomic background in order to more clearly understand and predict patients' individual course of disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14256","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T19:51:23Z","timestamp":1600458683000},"page":"578-585","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Prevalence and potential biological role of <i>TERT<\/i> amplifications in <i>ALK<\/i> translocated adenocarcinoma of the lung"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8815-1177","authenticated-orcid":false,"given":"Christina","family":"Alidousty","sequence":"first","affiliation":[{"name":"Institute of Pathology University Hospital Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolai","family":"Duerbaum","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Hospital Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svenja","family":"Wagener\u2010Ryczek","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Hospital Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Till","family":"Baar","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Institute of Medical Statistics and Computational Biology University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciano G","family":"Martelotto","sequence":"additional","affiliation":[{"name":"Monash Health Monash University Clayton Vic. 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