{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:48:52Z","timestamp":1787960932146,"version":"build-2784847793"},"reference-count":22,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672293"],"award-info":[{"award-number":["81672293"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972178"],"award-info":[{"award-number":["81972178"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Pulmonary nuclear protein of the testis (NUT) midline carcinoma (NMC) is a aggressive cancer with t (15, 19) translocation. Here we present the clinicopathological characteristics and molecular genetics alterations of primary pulmonary NMC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fluorescence in situ hybridization (FISH) assay was performed to evaluate <jats:italic>NUT<\/jats:italic> translocation. Next generation sequencing (NGS) was performed to investigate genomic landscape. A panel of 289 lung cancer tissues with undifferentiation was retrospectively screened for <jats:italic>NUT<\/jats:italic> expression by immunohistochemical (IHC) assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 2136 lung cancer samples were reviewed. We consecutively identified 12 cases of primary pulmonary NMC. Computed tomography revealed centrally located bulky lung mass with ipsilateral mediastinal lymph node and pleural involvements. Tumor cells presented diffuse poor differentiation and focal squamous differentiation with positive <jats:italic>NUT<\/jats:italic> expression. <jats:italic>NUT<\/jats:italic> rearrangement was confirmed by FISH assay. Ten NMC samples were investigated by NGS. The most common alterations identified were <jats:italic>P53<\/jats:italic>, <jats:italic>PIK3CA<\/jats:italic>, <jats:italic>AUTS2<\/jats:italic>, <jats:italic>ITIH2<\/jats:italic>, and <jats:italic>CDKL5<\/jats:italic> genes. Pulmonary NMC exhibited increased activity of PI3K\/AKT pathway. In the screening study, <jats:italic>BRD4<\/jats:italic>\u2010<jats:italic>NUT<\/jats:italic> rearrangement was identified in two cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>NUT<\/jats:italic> rearrangement remains the gold standard in the diagnosis of pulmonary NMC. PI3K inhibition is a potential targeted therapy for pulmonary NMC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4096","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T07:40:41Z","timestamp":1629358841000},"page":"5757-5764","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Clinicopathological and molecular characterizations of pulmonary NUT midline carcinoma"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5013-6673","authenticated-orcid":false,"given":"Mian","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinge","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Guangzhou 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