Intrathoracic Carcinoma in an 11-Year-Old Girl Showing a Translocation t(15;19)

Kees, Ursula R.; Mulcahy, Marie T.; Willoughby, M. L. N.

doi:10.1097/00043426-199124000-00011

Cited by 145 publications

(132 citation statements)

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“…Interestingly, in addition to the association of BRD4-NUT and ZNF532 proteins in 797TRex patient cells, we found that the ZNF532 locus is a binding target for BRD4-NUT. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis using anti-NUT antibodies revealed strong enrichment over or adjacent to the ZNF532 locus in a variety of NMC cells, including TC-797, 797TRex, 10-15 (16), and PER-403 (17), all of which harbor a BRD4-NUT fusion, and also 10326 cells, which carry a BRD3-NUT translocation (7) (Fig. 2C).…”

Section: Ep300mentioning

confidence: 99%

Ectopic protein interactions within BRD4–chromatin complexes drive oncogenic megadomain formation in NUT midline carcinoma

Alekseyenko

Walsh

Zee

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

110

167

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To investigate the mechanism that drives dramatic mistargeting of active chromatin in NUT midline carcinoma (NMC), we have identified protein interactions unique to the BRD4-NUT fusion oncoprotein compared with wild-type BRD4. Using cross-linking, affinity purification, and mass spectrometry, we identified the EP300 acetyltransferase as uniquely associated with BRD4 through the NUT fusion in both NMC and non-NMC cell types. We also discovered ZNF532 associated with BRD4-NUT in NMC patient cells but not detectable in 293T cells. EP300 and ZNF532 are both implicated in feed-forward regulatory loops leading to propagation of the oncogenic chromatin complex in BRD4-NUT patient cells. Adding key functional significance to our biochemical findings, we independently discovered a ZNF532-NUT translocation fusion in a newly diagnosed NMC patient. ChIP sequencing of the major players NUT, ZNF532, BRD4, EP300, and H3K27ac revealed the formation of ZNF532-NUT-associated hyperacetylated megadomains, distinctly localized but otherwise analogous to those found in BRD4-NUT patient cells. Our results support a model in which NMC is dependent on ectopic NUT-mediated interactions between EP300 and components of BRD4 regulatory complexes, leading to a cascade of misregulation.BioTAP-XL | hyperacetylation | ZNF532-NUT | topological domains | BRD4

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Section: Ep300mentioning

confidence: 99%

Ectopic protein interactions within BRD4–chromatin complexes drive oncogenic megadomain formation in NUT midline carcinoma

Alekseyenko

Walsh

Zee

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

110

167

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“…In 1991, two cases of carcinoma were described involving the thorax that were shown to have t (15;19) [1,2]. Both involved the mediastinum and were considered thymic in origin.…”

Section: Introductionmentioning

confidence: 99%

“…Overt squamous differentiation was not identified in these cases. Tumor cells typically appear polyhedral [1,14]. Intermediate junctions and desmosomes are seen, consistent with epithelial differentiation.…”

Section: Introductionmentioning

confidence: 99%

A Review of NUT Midline Carcinoma

Stelow

2011

Head and Neck Pathol

115

130

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“…NMCs are genetically simple, with NUT translocation generally the lone demonstrable karyotypic abnormality. [1][2][3]6,7,9,10 Given this, it can be assumed that the resulting fusion protein is pathogenetically fundamental. This hypothesis is given credence by recent siRNA experiments in NMC cell lines, in which BRD4-NUT knockdown resulted in striking squamous differentiation and growth arrest.…”

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confidence: 99%

The cytologic features of NUT midline carcinoma

Bellizzi

Bruzzi

French

et al. 2009

Cancer Cytopathology

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BACKGROUND:Nuclear protein in testis (NUT) midline carcinoma (NMC) represents an aggressive, high‐grade carcinoma typically involving the upper aerodigestive tract or mediastinum. Although the tumor was originally noted in young persons, we have subsequently identified 5 adult cases. To our knowledge, the cytology of NMC has not been systematically described.METHODS:We recently published a series of NMCs identified by fluorescent in situ hybridization for characteristic NUT rearrangement. Three of these patients had undergone fine‐needle aspiration. Patient age, sex, primary tumor location, and aspiration site were noted. Cases were assessed for the following: cellularity, architecture, cytoplasm, cell size, nuclear contours, nucleoli, chromatin, anisonucleosis/cytosis, mitotic activity, background, and nuclear crush.RESULTS:The 3 cases occurred in 2 women and 1 man, ages 31‐79 years. Primaries involved the sinonasal tract (2) and larynx. Aspirates were of right neck masses (2) and supraclavicular lymph node. Smears were highly cellular and generally noncohesive. Cytoplasm was scant/delicate, although occasional cells with denser cytoplasm were noted in 1 case. Cells were 2‐3 times the diameter of a small lymphocyte with irregular nuclear contours, discrete nucleoli, and fine/granular to vesicular chromatin. Anisonucleosis/cytosis was slight to moderate. Mitotic figures were noted in each case. The background contained naked nuclei and karyorrhectic debris; nuclear crush was noted.CONCLUSIONS:NMCs exhibit cytologic features of a poorly differentiated or undifferentiated carcinoma. Although reports mention squamous differentiation as a histologic feature, it is typically focal, and overt squamous differentiation was not identified in our cases. Given morphologic overlap with other high‐grade carcinomas, diagnosis requires a high index of suspicion. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.

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Intrathoracic Carcinoma in an 11-Year-Old Girl Showing a Translocation t(15;19)

Cited by 145 publications

References 0 publications

Ectopic protein interactions within BRD4–chromatin complexes drive oncogenic megadomain formation in NUT midline carcinoma

Ectopic protein interactions within BRD4–chromatin complexes drive oncogenic megadomain formation in NUT midline carcinoma

A Review of NUT Midline Carcinoma

The cytologic features of NUT midline carcinoma

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