{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:00:22Z","timestamp":1792202422846,"version":"4.4.0"},"reference-count":106,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"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>Nuclear protein in testis (NUT) carcinoma is a rare, highly aggressive, poorly differentiated carcinoma occurring mostly in adolescents and young adults. This tumor usually arises from the midline structures of the thorax, head, and neck, and exhibits variable degrees of squamous differentiation. NUT carcinoma is defined by the presence of a <jats:italic>NUTM1<\/jats:italic> (15q14) rearrangement with multiple other genes. In about 70-80% of the cases, <jats:italic>NUTM1<\/jats:italic> is involved in a balanced translocation with the <jats:italic>BRD4<\/jats:italic> gene (19p13.12), leading to a <jats:italic>BRD4-NUTM1<\/jats:italic> fusion oncogene. Other variant rearrangements include <jats:italic>BRD3-NUTM1<\/jats:italic> fusion (~15-20%) and <jats:italic>NSD3-NUTM1<\/jats:italic> fusion (~6%), among others. The diagnosis of NUT carcinoma requires the detection of nuclear expression of the NUT protein by immunohistochemistry. Additional methods for diagnosis include the detection of a <jats:italic>NUTM1<\/jats:italic> rearrangement by fluorescence <jats:italic>in situ<\/jats:italic> hybridization or by reverse transcriptase PCR. NUT carcinoma is usually underrecognized due to its rarity and lack of characteristic histological features. Therefore, the goal of this review is to provide relevant recent information regarding the clinicopathologic features of NUT carcinoma, the role of the multiple <jats:italic>NUTM1<\/jats:italic> gene rearrangements in carcinogenesis, and the impact of understanding these underlying molecular mechanisms that may result in the development of possible novel targeted therapies.<\/jats:p>","DOI":"10.3389\/fonc.2022.860830","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T05:37:46Z","timestamp":1647409066000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":62,"title":["NUT Carcinoma: Clinicopathologic Features, Molecular Genetics and 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