TY - JOUR
T1 - NUT midline carcinoma
T2 - An aggressive intrathoracic neoplasm
AU - Parikh, Sameer A.
AU - French, Christopher A.
AU - Costello, Brian A.
AU - Marks, Randolph S.
AU - Dronca, Roxana S.
AU - Nerby, Craig L.
AU - Roden, Anja C.
AU - Peddareddigari, Vijay G.
AU - Hilton, John
AU - Shapiro, Geoffrey I.
AU - Molina, Julian R.
N1 - Funding Information:
Disclosure: Dr. Costello is a member of the Data Safety and Monitoring Board for a phase 1 trial sponsored by Synergene Therapeutics and has received financial support for the same. Dr. Peddareddigari is currently employed by GlaxoSmithKline and owns stock in the company. The other authors declare no conflict of interest.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Bromodomain and extra terminal inhibitor
KW - Bromodomain containing 4 nuclear protein in testis
KW - Epigenetics
KW - Histone deacetylase inhibitors
KW - Poorly differentiated neoplasm
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U2 - 10.1097/JTO.0b013e3182a00f41
DO - 10.1097/JTO.0b013e3182a00f41
M3 - Article
C2 - 24457244
AN - SCOPUS:84892379241
SN - 1556-0864
VL - 8
SP - 1335
EP - 1338
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 10
ER -