{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:11:04Z","timestamp":1753891864232,"version":"3.41.2"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p><jats:italic>NTRK<\/jats:italic> fusions are validated oncogenic drivers of various adult and pediatric tumor types, including thyroid cancer, and serve as a therapeutic target. Recently, tropomyosin receptor kinase (TRK) inhibitors, such as entrectinib and larotrectinib, display promising therapeutic efficacy in <jats:italic>NTRK<\/jats:italic>-positive solid tumors. Although some <jats:italic>NTRK<\/jats:italic> fusion partners have been identified in thyroid cancer, the spectrum of <jats:italic>NTRK<\/jats:italic> fusion is not fully characterized. In this study, a dual <jats:italic>NTRK3<\/jats:italic> fusion was identified by targeted RNA-Seq in a 47-year-old female patient with papillary thyroid carcinoma. The patient harbors a novel in-frame fusion between <jats:italic>NTRK3<\/jats:italic> exon 13 and <jats:italic>AJUBA<\/jats:italic> exon 2, co-existing with a known in-frame fusion between <jats:italic>ETV6<\/jats:italic> exon 4 and <jats:italic>NTRK3<\/jats:italic> exon 14. The dual <jats:italic>NTRK3<\/jats:italic> fusion was validated by Sanger sequencing and fluorescence <jats:italic>in situ<\/jats:italic> hybridization (FISH) but lack TRK protein expression as defined by pan-TRK immunohistochemistry (IHC). We supposed the pan-TRK IHC result to be falsely negative. In conclusion, we present the first case of a novel <jats:italic>NTRK3-AJUBA<\/jats:italic> fusion co-existing with a known <jats:italic>ETV6-NTRK3<\/jats:italic> fusion in thyroid cancer. These findings extend the spectrum of translocation partners in <jats:italic>NTRK3<\/jats:italic> fusion, and the effect of dual <jats:italic>NTRK3<\/jats:italic> fusion on TRK inhibitor therapy and prognosis needs long-term follow-up.<\/jats:p>","DOI":"10.3389\/fonc.2023.1123812","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T10:39:00Z","timestamp":1682678340000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case Report: Identification of a novel NTRK3-AJUBA fusion co-existing with ETV6-NTRK3 fusion in papillary thyroid 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