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Although ALK rearrangements, particularly\n                    <jats:italic>STRN::ALK<\/jats:italic>\n                    fusions, have been described in thyroid carcinomas, their biological and clinical significance in oncocytic thyroid neoplasms remains unclear. This study investigated\n                    <jats:italic>STRN<\/jats:italic>\n                    exon 3-\n                    <jats:italic>ALK<\/jats:italic>\n                    exon 20-derived transcripts in 56 oncocytic thyroid neoplasms using RT-PCR, followed by cloning and Sanger sequencing of positive cases. Transcript-positive cases were further evaluated by fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and in silico structural modeling.\n                    <jats:italic>STRN<\/jats:italic>\n                    ::\n                    <jats:italic>ALK<\/jats:italic>\n                    -derived transcripts were detected in 9 of 56 tumors; however, their frequency reflected the combined detection of distinct transcript architectures. Only 2 of 56 tumors (3.6%) harbored canonical in-frame\n                    <jats:italic>STRN<\/jats:italic>\n                    ::\n                    <jats:italic>ALK<\/jats:italic>\n                    fusions, whereas 7 of 56 tumors (12.5%) contained noncanonical out-of-frame variants. Although ALK rearrangement by FISH was confirmed in all transcript-positive tumors irrespective of transcript architecture, detectable ALK protein expression by IHC was observed only in tumors harboring canonical in-frame fusions, whereas all noncanonical variants lacked detectable ALK protein expression. Structural modeling was concordant with these observations, suggesting preservation of kinase-domain features in canonical fusions and predicted disruption in noncanonical variants. Overall,\n                    <jats:italic>STRN::ALK<\/jats:italic>\n                    transcripts in oncocytic thyroid neoplasms exhibit marked architectural heterogeneity with distinct ALK protein expression patterns. ALK FISH-positive\/IHC-negative cases should be interpreted cautiously, as they may not represent biologically equivalent ALK-driven neoplasia, with uncertain therapeutic relevance. Integrated molecular and protein-level assessment may support interpretation of ALK alterations in oncocytic thyroid neoplasms.\n                  <\/jats:p>","DOI":"10.1007\/s12022-026-09924-0","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:02:34Z","timestamp":1782964954000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct ALK Expression Patterns Are Associated with Canonical and Noncanonical STRN::ALK Transcript Architectures in Oncocytic Thyroid Neoplasms"],"prefix":"10.1007","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0626-5352","authenticated-orcid":false,"given":"Debora Mota Dias","family":"Thomaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0114-4578","authenticated-orcid":false,"given":"Thais Biude","family":"Mendes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4637-1240","authenticated-orcid":false,"given":"Thaise Nayane Ribeiro","family":"Carneiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7452-5756","authenticated-orcid":false,"given":"Luiza","family":"Sisdelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2009-9079","authenticated-orcid":false,"given":"Ana Carolina de Jesus","family":"Paniza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0903-8035","authenticated-orcid":false,"given":"Andr\u00e9 Uchimura","family":"Bastos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0156-8274","authenticated-orcid":false,"given":"Janete Maria","family":"Cerutti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"9924_CR1","doi-asserted-by":"publisher","first-page":"168","DOI":"10.3390\/biomedicines14010168","volume":"14","author":"F Vaio","year":"2026","unstructured":"Vaio F, Moliterni C, Mardente S, Misasi R, Mari E (2026) State of the Art on Thyroid Cancer Biology and Oncology. 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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The requirement for informed consent was waived due to the retrospective nature of the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Informed consent was waived by the institutional review board because of the retrospective nature of this study, which used anonymous clinical data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors approved for the publication of this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"27"}}