{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T09:49:54Z","timestamp":1782899394905,"version":"3.54.5"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Nuclear protein in testis (NUT) carcinoma (NC) is an extremely rare and highly aggressive tumor. Non-canonical NC patients frequently have unique clinicopathological characteristics in terms of location, molecular alteration, and outcome, with morphological overlap with other tumors. Here, we report and summarize the non-canonical clinicopathological features of three unusual NC patients harboring\n                      <jats:italic>BRD3::NUTM1<\/jats:italic>\n                      or\n                      <jats:italic>WWTR1::NUTM1<\/jats:italic>\n                      gene rearrangement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The data of three patients with NC who were diagnosed between 2019 and 2022 at the Department of Pathology at West China Hospital or the Sichuan Kingmed Center for Clinical Laboratory were collected. Immunohistochemistry (IHC), fluorescence\n                      <jats:italic>in situ<\/jats:italic>\n                      hybridization (FISH), and RNA sequencing were performed. A literature review was conducted for NC patients with non-canonical features.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All three NC patients were male and aged between 31 and 60 years. The primary sites were the gastric corpus, nasal cavity, and subcutaneous tissue of the calvaria vertex. Histologically, two patients harbored NC with glandular differentiation, and one harbored NC with small cell carcinoma-like morphology. IHC revealed positivity for Pan-CK (cytokeratin) (PCK) (3\/3), Epithelial membrane antigen (EMA) (3\/3), Cytokeratin 5\/6 (CK5\/6) (3\/3), and P63 (2\/3). The Ki-67 index ranged from 20% to 40%. The remaining IHC markers were negative. RNA sequencing revealed\n                      <jats:italic>BRD3::NUTM1<\/jats:italic>\n                      fusion in two patients and\n                      <jats:italic>WWTR1::NUTM1<\/jats:italic>\n                      fusion in one patient.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In our study, the clinicopathological features of NC in patients with rare molecular alterations are reported and summarized. As increasing numbers of\n                      <jats:italic>NUTM1<\/jats:italic>\n                      -rearranged tumors with diverse histologic phenotypes have been reported, the traditional classification of NC as a purely epithelial malignancy may warrant reconsideration. Non-canonical NC needs to be further reported, integrated, and classified to precisely guide targeted therapy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1828484","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T09:24:44Z","timestamp":1782897884000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Expanding the spectrum of non-canonical NUT carcinoma: clinicopathological and molecular characterization of BRD3::NUTM1 and WWTR1::NUTM1 fusion variants"],"prefix":"10.3389","volume":"16","author":[{"given":"Zuoyu","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Pathology of West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology of West China Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Department of Pathology of West China Tianfu Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Zhai","sequence":"additional","affiliation":[{"name":"Lung Cancer Center and Institute of West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology of West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology of West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Tang","sequence":"additional","affiliation":[{"name":"Pathological Diagnosis Center, Sichuan Kingmed Center for Clinical Laboratory Co., Ltd.","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Huang","sequence":"additional","affiliation":[{"name":"Pathological Diagnosis Center, Sichuan Kingmed Center for Clinical Laboratory Co., Ltd.","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology of West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology of West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuexue","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology of West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Bao","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pathology of West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongni","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pathology, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pathology of West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiya","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology of West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/pin.12727","article-title":"Nut carcinoma: clinicopathologic features, pathogenesis, and treatment","volume":"68","author":"French","year":"2018","journal-title":"Pathol Int"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2019.102826","article-title":"Nut midline carcinoma: current concepts and future perspectives of 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