{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:24:35Z","timestamp":1793118275508,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100019543","name":"Kristen Ann Carr Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 CA217694"],"award-info":[{"award-number":["P50 CA217694"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017050","name":"Cycle for Survival","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2026,9]]},"abstract":"Abstract<\/jats:title>\n \n NTRK<\/jats:italic>\n fusions drive the pathogenesis of a distinctive group of mesenchymal neoplasms with significant impact on classification and targeted therapy. However, unexpected\n NTRK<\/jats:italic>\n fusions have been reported in other sarcoma entities, raising uncertainty over their specificity and clinical management. Herein, we investigate the incidence and structural variants of\n NTRK<\/jats:italic>\n fusions among a large clinicopathologic and molecular sarcoma cohort. The goal was to distinguish primary driver\n NTRK<\/jats:italic>\n fusions from potential passenger events and correlate with sarcoma histotypes.\n NTRK1\u20103<\/jats:italic>\n fusions were queried across a large spectrum of sarcomas, profiled by targeted DNA and\/or RNAseq. Fusions were classified as oncogenic when\n NTRK<\/jats:italic>\n was the 3\u2032 partner, in\u2010frame, retained kinase domain (KD), and\/or RNAseq confirmation; fusions of uncertain significance (FUS) when out\u2010of\u2010frame, lacking full KD, and\/or RNAseq negative. We identified 48 cases with\n NTRK<\/jats:italic>\n fusions, detected either by pathologist\u2010initiated RNAseq for diagnosis (\n n<\/jats:italic>\n \u2009=\u200927) or by clinician\u2010initiated DNAseq for therapeutic target discovery (\n n<\/jats:italic>\n \u2009=\u200921). For the latter subset, reflex RNAseq was activated for confirmation. Integrated review confirmed 33 (69%) oncogenic fusions. Remaining were FUS, apart from one indeterminate. In all except three cases, oncogenic fusions occurred in canonical\n NTRK<\/jats:italic>\n \u2010driven histotypes. In contrast,\n NTRK<\/jats:italic>\n FUS were detected in various pathologic entities, including well\u2010differentiated\/dedifferentiated liposarcoma (\n n<\/jats:italic>\n \u2009=\u20099, 60%), two osteosarcoma, and single cases of other subtypes.\n NTRK1<\/jats:italic>\n fusions were the most common in both oncogenic and FUS groups (61%, 67%).\n CDKN2A\/B<\/jats:italic>\n deletions were observed mostly in oncogenic\n NTRK1<\/jats:italic>\n fusions (71%), while\n MDM2\/CDK4<\/jats:italic>\n amplifications in the\n NTRK1<\/jats:italic>\n FUS. The FUS group demonstrated lower\n NTRK<\/jats:italic>\n mRNA expression, with a mean of \u22124.60,\n p<\/jats:italic>\n \u2009<\u20090.001. Pan\u2010TRK immunohistochemistry was positive in cases with oncogenic\n NTRK<\/jats:italic>\n fusions, and negative in FUS cases. Only two\u2010thirds of\n NTRK<\/jats:italic>\n fusions detected were functional drivers, mostly from pathologist\u2010driven testing of suggestive histotypes. In contrast, genomic profiling in complex sarcomas often yields passenger FUS, lacking functional impact.\n <\/jats:p>","DOI":"10.1002\/2056-4538.70111","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:00:34Z","timestamp":1785751234000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Not all\n \n NTRK<\/i>\n <\/scp>\n fusions in mesenchymal neoplasia are driver events: implications on classification and targeted therapy"],"prefix":"10.1002","volume":"12","author":[{"given":"Mohamed A","family":"Yakoub","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purvil","family":"Sukhadia","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4540-6990","authenticated-orcid":false,"given":"Carla","family":"Saoud","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meera","family":"Hameed","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9717-8205","authenticated-orcid":false,"given":"Cristina R","family":"Antonescu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz383"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0113-0"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000675"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22846"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22877"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.32074\/1591-951X-213"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/14796694.2025.2597405"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004088"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2018.05.007"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2014.12.006"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2022.06.030"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyaf401"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-026-06426-8"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-025-04324-x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO-25-00612"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714448"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.02.019"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.15218"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-021-00206-y"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0118-3"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14842"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14295"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0324-7"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.08.2232"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.6140"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjp2.158"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14443"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2025.105555"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30691-6"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.35036"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-0571"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-0507"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-15-0940"}],"container-title":["The 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