NUT Carcinoma: Clinicopathologic features, pathogenesis, and treatment. Issue 11 (26th October 2018)

• Record Type: Journal Article
• Authors: French, Christopher A.
• Is Part Of: Pathology international. Volume 68:Issue 11(2018)
• Page Start: 583
• Page End: 595
• Publication Date: 2018-10-26
• Subjects: BET inhibitor -- BRD3 -- BRD4‐NUT -- differentiation therapy -- histone acetyl‐transferase -- histone deacetylase inhibitor -- NSD3 -- ZNF532 -- NUT carcinoma -- NUT midline carcinoma -- www.NMCRegistry.org; Pathology -- Periodicals; 616.07
• DOI: 10.1111/pin.12727
• Languages: English
• ISSNs: 1320-5463

Abstract

Abstract : NUT carcinoma (NC) is a rare, aggressive subtype of squamous cell carcinoma defined by rearrangement of the NUTM1 (aka NUT ) gene. NC is driven by NUT‐fusion oncoproteins resulting from chromosomal translocation, most commonly BRD4‐NUT. This is a nearly uniformly lethal cancer affecting patients of all ages, but predominantly teens and young adults. The cell of origin is unknown, but NC most commonly arises within the thorax and head and neck. NC typically consists of sheets of monomorphic primitive round cells that can exhibit focal abrupt squamous differentiation. Diagnosis of NC is easy, and can be established by positive NUT nuclear immunohistochemical staining. Though characterization of the NUTM1‐fusion gene is desirable by molecular analysis, it is not required for the diagnosis. The increasingly widespread availability of the NUT diagnostic test is leading to increasing diagnoses of this vastly underdiagnosed disease. The NUT midline carcinoma registry (www.NMCRegistry.org ) serves as a central repository that has provided the main source of clinical and outcomes data for NC. Currently there is no effective therapy for NC, however small molecules directly targeting the BRD4 portion of BRD4‐NUT, termed BET bromodomain inhibitors, have shown activity.