{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:09:25Z","timestamp":1789124965481,"version":"build-2803163510"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Anaplastic lymphoma kinase (\n                    <jats:italic>ALK<\/jats:italic>\n                    ) rearrangements define a distinct molecular subset of non\u2013small cell lung cancer (NSCLC) that is highly sensitive to\n                    <jats:italic>ALK<\/jats:italic>\n                    tyrosine kinase inhibitors (TKIs). While canonical EML4::\n                    <jats:italic>ALK<\/jats:italic>\n                    fusions are well characterized, the clinical significance of rare noncanonical ALK rearrangements and structural alterations remains incompletely understood and may present interpretive challenges across sequencing platforms. Here, we present the case of a 61-year-old never-smoker with metastatic lung adenocarcinoma harboring a rare\n                    <jats:italic>ALK<\/jats:italic>\n                    structural deletion identified through complementary genomic profiling. Initial comprehensive genomic profiling identified an EML4::\n                    <jats:italic>ALK<\/jats:italic>\n                    rearrangement, while subsequent orthogonal DNA\/RNA genomic based profiling identified a rare WDR43::ALK structural deletion resulting in a fusion transcript. ALK immunohistochemistry demonstrated ALK protein expression, supporting oncogenic\n                    <jats:italic>ALK<\/jats:italic>\n                    pathway activation despite the atypical genomic architecture. The patient was treated with frontline alectinib and achieved a rapid, deep, and durable response with sustained systemic and intracranial disease control for more than six years. This case highlights the importance of integrative genomic interpretation in precision oncology and supports that rare ALK structural alterations may retain clinically meaningful sensitivity to modern ALK inhibition. As comprehensive sequencing becomes increasingly incorporated into routine oncologic practice, correlation of genomic findings with protein expression, clinicopathologic features, and treatment response may help determine the therapeutic relevance of unconventional\n                    <jats:italic>ALK<\/jats:italic>\n                    alterations.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1886919","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T04:25:04Z","timestamp":1785990304000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Complete response and prolonged survival to alectinib in a NSCLC patient with metastases harboring a rare WDR43::ALK structural deletion"],"prefix":"10.3389","volume":"16","author":[{"given":"Lauren","family":"Epler","sequence":"first","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanny","family":"Velasquez","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isa","family":"Mambetsariev","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Arias-Romero","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Fricke","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biology, Northwestern University","place":["Chicago,\u00a0IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razmig","family":"Babikian","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linh","family":"Ngo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonidas","family":"Arvanitis","sequence":"additional","affiliation":[{"name":"Department of Pathology, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit A.","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope Phoenix","place":["Goodyear, AZ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz A.","family":"Urgun","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Gruber","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Afkhami","sequence":"additional","affiliation":[{"name":"Department of Pathology, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Salgia","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center","place":["Duarte, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05945","article-title":"Identification of the transforming EML4\u2013ALK fusion gene in non-small-cell lung 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factors linking transcription and processing of pre-rRNA to NOR chromatin is UBF-dependent and occurs independent of transcription in human cells","volume":"21","author":"Prieto","year":"2007","journal-title":"Genes Dev"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/science.abj5338","article-title":"Nucleolar maturation of the human small subunit processome","volume":"373","author":"Singh","year":"2021","journal-title":"Science"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2015-0497","article-title":"Comprehensive genomic profiling identifies a subset of crizotinib-responsive ALK -rearranged non-small cell lung cancer not detected by fluorescence in situ hybridization","volume":"21","author":"Ali","year":"2016","journal-title":"Oncologist"},{"key":"B8","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.jmoldx.2016.10.002","article-title":"Standards and guidelines for the interpretation and reporting of sequence variants in cancer","volume":"19","author":"Li","year":"2017","journal-title":"J Mol Diagn"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S282933","article-title":"STRN-ALK fusion in lung adenocarcinoma with excellent response upon alectinib treatment: a case report and literature review","volume":"13","author":"Su","year":"2020","journal-title":"Onco Targets Ther"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16897","article-title":"Mixed responses to first-line alectinib in non-small cell lung cancer patients with rare ALK gene fusions: a case series and literature review","volume":"25","author":"Li","year":"2021","journal-title":"J Cell Mol Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1594072","article-title":"Case report: a rare case of ALK-KIF5B gene fusion benefited from treatment with lorlatinib","volume":"15","author":"Luo","year":"2025","journal-title":"Front Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.23005","article-title":"Clinicopathological features and resistance mechanisms in HIP1-ALK-rearranged lung cancer: a multicenter study","volume":"61","author":"Kang","year":"2022","journal-title":"Genes Chromosomes Cancer"},{"key":"B13","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.lungcan.2017.10.011","article-title":"GCC2-ALK as a targetable fusion in lung adenocarcinoma and its enduring clinical responses to ALK inhibitors","volume":"115","author":"Jiang","year":"2018","journal-title":"Lung Cancer"},{"key":"B14","doi-asserted-by":"publisher","first-page":"12510","DOI":"10.1038\/s41598-017-12679-8","article-title":"Detection of known and novel ALK fusion transcripts in lung cancer patients using next-generation sequencing approaches","volume":"7","author":"Vendrell","year":"2017","journal-title":"Sci Rep"}],"updated-by":[{"DOI":"10.3389\/fonc.2026.1961716","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000}}],"container-title":["Frontiers in 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