{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T14:56:29Z","timestamp":1781016989599,"version":"3.54.1"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Although molecular tests developed for a growing list of oncogenic alterations have significantly aided in the classification of head and neck carcinomas, tumours in which prototypical histologic and immunophenotypic features are lacking or only partially developed continue to pose diagnostic challenges. Searching for known diagnostic and therapeutic targets by clinical next\u2010generation sequencing (NGS) assays can often lead to new discoveries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>We present our institutional experience in applying targeted RNA NGS in 36 head and neck carcinomas that were morphologically difficult to classify between 2016 and 2023. The patients ranged in age from 5 to 83\u2009years (median, 64), with the majority of tumors occurring in the major salivary glands and the sinonasal tract. Overall, seven (19%) cases showed unusual gene rearrangements, including five novel alterations: <jats:italic>MON2<\/jats:italic>::<jats:italic>STAT6<\/jats:italic> in a hard palate adenocarcinoma with mucinous features, <jats:italic>POC5<\/jats:italic>::<jats:italic>RAF1<\/jats:italic> in apocrine intraductal carcinoma of the lacrimal gland, <jats:italic>EWSR1<\/jats:italic>::<jats:italic>CDADC1<\/jats:italic> fusion in a basaloid carcinoma of the submandibular gland, <jats:italic>NFATC2<\/jats:italic>::<jats:italic>NUTM2B<\/jats:italic> in myoepithelial carcinoma, and <jats:italic>NSD3<\/jats:italic>::<jats:italic>NCOA2<\/jats:italic> fusion in a peculiar high\u2010grade carcinoma with a peritheliomatous growth pattern, and focal myogenic differentiation. Potential therapeutic actionability was identified in three cases (<jats:italic>RAF1<\/jats:italic> and <jats:italic>FGFR2<\/jats:italic> fusions).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings broaden the current spectrum of gene rearrangements in head and neck carcinomas and support the utility of clinical NGS in identifying unusual, actionable alterations in diagnostically challenging cases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15380","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T08:46:42Z","timestamp":1733302002000},"page":"728-741","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Targeted <scp>RNA<\/scp> sequencing in diagnostically challenging head and neck carcinomas identifies novel <i>MON2<\/i>::<i>STAT6<\/i>, <i>NFATC2<\/i>::<i>NUTM2B<\/i>, <i>POC5<\/i>::<i>RAF1,<\/i> and <i>NSD3<\/i>::<i>NCOA2<\/i> gene fusions"],"prefix":"10.1111","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8289-7418","authenticated-orcid":false,"given":"Ying\u2010Hsia","family":"Chu","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2974-3046","authenticated-orcid":false,"given":"Nora","family":"Katabi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6079-0871","authenticated-orcid":false,"given":"Purvil","family":"Sukhadia","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3308-1727","authenticated-orcid":false,"given":"Kerry A","family":"Mullaney","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8288-7687","authenticated-orcid":false,"given":"Michael","family":"Zaidinski","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4496-906X","authenticated-orcid":false,"given":"Jeniffer R","family":"Cracchiolo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Head and Neck Service Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4638-9835","authenticated-orcid":false,"given":"Bin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2802-8489","authenticated-orcid":false,"given":"Ronald A","family":"Ghossein","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6885-3742","authenticated-orcid":false,"given":"Alan L","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4099-1034","authenticated-orcid":false,"given":"Sara E","family":"DiNapoli","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9055-7213","authenticated-orcid":false,"given":"Marc","family":"Ladanyi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4905-8946","authenticated-orcid":false,"given":"Snjezana","family":"Dogan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0008-8"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000932"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3182772a15"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22195"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001535"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001065"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000952"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-020-01128-0"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2021.05.004"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-0225"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0175-7"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2014.12.006"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3466"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.15099"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2509"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2014.11.018"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1952-6"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2522"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep03362"},{"key":"e_1_2_13_22_1","first-page":"5988","article-title":"Microrna\u2010133a\u20105p inhibiting metastatic capacity of renal clear cell carcinoma through regulating mon2","volume":"24","author":"Li P","year":"2020","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.23333"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.406"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-818"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.03.050"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001875"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2017.12.024"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10014-018-0333-0"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-022-01444-7"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2024.102154"},{"key":"e_1_2_13_32_1","unstructured":"MitelmanF JohanssonB MertensF.Mitelman database of chromosome aberrations and gene fusions in cancer.2023."},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-024-01653-2"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.27587"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200608000-00013"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.21.00303"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI123089"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201845766"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.036"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2016.02.048"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-1970-0"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002023"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004088"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-23-0816"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1115528109"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-2184"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01178-z"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.635172"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9386390"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hpr.2022.300680"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2018.03.020"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001441"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000538"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5899"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-14-0014"},{"key":"e_1_2_13_57_1","first-page":"726","article-title":"Structure, activity and function of the nsd3 protein lysine methyltransferase","volume":"11","author":"Rathert P","year":"2021","journal-title":"Lifestyles (Basel, Switzerland)"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.10.033"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2022.05.015"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01180-1"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/jncics\/pkz093"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.15380","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T00:22:36Z","timestamp":1743812556000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.15380"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,4]]},"references-count":60,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/his.15380"],"URL":"https:\/\/doi.org\/10.1111\/his.15380","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,4]]},"assertion":[{"value":"2024-08-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}