NUT midline carcinoma: an aggressive intrathoracic neoplasm.

Abstract

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a poorly differentiated squamous cell carcinoma that is characterized by a balanced translocation between chromosomes 15 and 19 [t(15;19)(q14;p13.1)]. This genetic aberration results in the fusion of the NUT gene on chromosome 15 to the bromodomain containing 4 (BRD4) gene on chromosome 19. The resultant BRD4-NUT fusion oncogene leads to global hypoacetylation and transcriptional repression of genes required for differentiation." Although it was first reported in 1991 by Kubonishi et al., awareness of this condition remains low and the diagnosis is overlooked initially in a number of patients. A 36-year-old man complained of cough and right-sided chest pain for 3 weeks before presentation. Imaging studies revealed a right hilar mass, and a bronchoscopic biopsy was consistent with an aggressive poorly differentiated neoplasm. A combination of cisplatin, ifosfamide, and etoposide was administered for two cycles without any improvement. A repeat core biopsy showed focal squamous differentiation; and given the clinical presentation along with the histologic features, NMC was considered in the differential diagnosis. Immunohistochemical staining for NUT was positive, and dual-color break-apart fluorescence in situ hybridization demonstrated BRD4-NUT rearrangement, thereby confirming a diagnosis of NMC. Our patient was subsequently enrolled on a phase 1 clinical trial of a novel, orally bioavailable bromodomain and extra terminal inhibitor, GSK525762 (NCT01587703). This report illustrates the challenges in diagnosing this rare malignancy, and highlights new treatment options for these patients.

DOI: 10.1097/JTO.0b013e3182a00f41
0100200300201520162017
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@article{Parikh2013NUTMC, title={NUT midline carcinoma: an aggressive intrathoracic neoplasm.}, author={Sameer A Parikh and Christopher Alexander French and Brian Addis Costello and Randolph S. Marks and Roxana Stefania Dronca and Craig L Nerby and Anja Christiane Roden and Vijay G R Peddareddigari and John Hilton and Geoffrey I. Shapiro and J. Molina}, journal={Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer}, year={2013}, volume={8 10}, pages={1335-8} }