NUT midline carcinoma: An aggressive intrathoracic neoplasm

Sameer A Parikh, Christopher A. French, Brian Costello, Randolph Stuart Marks, Roxana S Dronca, Craig L. Nerby, Anja Roden, Vijay G. Peddareddigari, John Hilton, Geoffrey I. Shapiro, Julian R Molina

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1335-1338
Number of pages4
JournalJournal of Thoracic Oncology
Volume8
Issue number10
DOIs
StatePublished - 2013

Fingerprint

Nuclear Proteins
Testis
Carcinoma
Chromosomes, Human, Pair 19
Chromosomes, Human, Pair 15
Neoplasms
Oncogene Fusion
Genes
Biopsy
Ifosfamide
Clinical Trials, Phase I
Etoposide
Chest Pain
Fluorescence In Situ Hybridization
Cough
Cisplatin
Squamous Cell Carcinoma
Differential Diagnosis
Color
Staining and Labeling

Keywords

  • Bromodomain and extra terminal inhibitor
  • Bromodomain containing 4 nuclear protein in testis
  • Epigenetics
  • Histone deacetylase inhibitors
  • Poorly differentiated neoplasm

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

NUT midline carcinoma : An aggressive intrathoracic neoplasm. / Parikh, Sameer A; French, Christopher A.; Costello, Brian; Marks, Randolph Stuart; Dronca, Roxana S; Nerby, Craig L.; Roden, Anja; Peddareddigari, Vijay G.; Hilton, John; Shapiro, Geoffrey I.; Molina, Julian R.

In: Journal of Thoracic Oncology, Vol. 8, No. 10, 2013, p. 1335-1338.

Research output: Contribution to journalArticle

Parikh, Sameer A ; French, Christopher A. ; Costello, Brian ; Marks, Randolph Stuart ; Dronca, Roxana S ; Nerby, Craig L. ; Roden, Anja ; Peddareddigari, Vijay G. ; Hilton, John ; Shapiro, Geoffrey I. ; Molina, Julian R. / NUT midline carcinoma : An aggressive intrathoracic neoplasm. In: Journal of Thoracic Oncology. 2013 ; Vol. 8, No. 10. pp. 1335-1338.
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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.",
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AU - Molina, Julian R

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