{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T12:59:18Z","timestamp":1775134758352,"version":"3.50.1"},"reference-count":26,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,12]],"date-time":"2020-07-12T00:00:00Z","timestamp":1594512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009647","name":"Ministry Of Health","doi-asserted-by":"publisher","award":["Ricerca Corrente"],"award-info":[{"award-number":["Ricerca Corrente"]}],"id":[{"id":"10.13039\/100009647","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: The Anaplastic Lymphoma Kinase (ALK) gene is known to be affected by several genetic alterations, such as rearrangement, amplification and point mutation. The main goal of this study was to comprehensively analyze ALK amplification (ALK-A) and ALK gene copy number gain (ALK-CNG) in a large cohort of non-small-cell lung cancer (NSCLC) patients in order to evaluate the effects on mRNA and protein expression. Methods: ALK locus number status was evaluated in 578 NSCLC cases by fluorescence in situ hybridization (FISH). In addition, ALK immunohistochemistry and ALK mRNA in situ hybridization were performed. Results: Out of 578 cases, 17 cases showed ALK-A. In addition, 14 cases presented ALK-CNG and 72 cases presented chromosome 2 polyploidy. None of those carrying ALK-A and -CNG showed either ALK immunohistochemical expression or ALK mRNA expression through in situ hybridization. We observed a high frequency of extra copies of the ALK gene. Conclusions: Our findings demonstrated that ALK-A is not involved in mRNA production and consequently is not involved in protein production; these findings support the hypothesis that ALK-A might not play a role in the pathogenesis of NSCLC, underlining the absence of a specific clinical application.<\/jats:p>","DOI":"10.3390\/ijms21144927","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T09:30:49Z","timestamp":1594719049000},"page":"4927","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Unproductive Effects of ALK Gene Amplification and Copy Number Gain in Non-Small-Cell Lung Cancer. ALK Gene Amplification and Copy Gain in NSCLC"],"prefix":"10.3390","volume":"21","author":[{"given":"Federica","family":"Zito Marino","sequence":"first","affiliation":[{"name":"Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania \u201cL. Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerardo","family":"Botti","sequence":"additional","affiliation":[{"name":"Pathology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS \u201cFondazione Pascale\u201d, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Aquino","sequence":"additional","affiliation":[{"name":"Pathology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS \u201cFondazione Pascale\u201d, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3010-3268","authenticated-orcid":false,"given":"Gabriella","family":"Gaudioso","sequence":"additional","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4510-5167","authenticated-orcid":false,"given":"Alessandro","family":"Palleschi","sequence":"additional","affiliation":[{"name":"Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danilo","family":"Rocco","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Oncology, AORN Dei Colli Monaldi, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosario","family":"Salvi","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Unit, AORN Dei Colli Monaldi, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Carolina","family":"Micheli","sequence":"additional","affiliation":[{"name":"Pathology Unit, AORN Dei Colli Monaldi, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"Micheli","sequence":"additional","affiliation":[{"name":"Pathology Unit, AORN Dei Colli Monaldi, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Morabito","sequence":"additional","affiliation":[{"name":"Thoracic Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS \u201cFondazione Pascale\u201d, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4150-8604","authenticated-orcid":false,"given":"Gaetano","family":"Rocco","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5959-016X","authenticated-orcid":false,"given":"Antonio","family":"Giordano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy"},{"name":"Sbarro Health Research Organization, Philadelphia, PA 19122, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossella","family":"De Cecio","sequence":"additional","affiliation":[{"name":"Pathology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS \u201cFondazione Pascale\u201d, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renato","family":"Franco","sequence":"additional","affiliation":[{"name":"Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania \u201cL. Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1242\/jcs.01183","article-title":"ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth","volume":"117","author":"Motegi","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1126\/science.8122112","article-title":"Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin\u2019s lymphoma","volume":"263","author":"Morris","year":"1994","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrc2291","article-title":"The anaplastic lymphoma kinase in the pathogenesis of cancer","volume":"8","author":"Chiarle","year":"2008","journal-title":"Nat. Rev. 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[2nd ed.]."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/14\/4927\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:50:36Z","timestamp":1760176236000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/14\/4927"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,12]]},"references-count":26,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["ijms21144927"],"URL":"https:\/\/doi.org\/10.3390\/ijms21144927","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,12]]}}}