NUT Gene Rearrangement in a Poorly-differentiated Carcinoma of the Submandibular Gland

Ziai, James; French, Chris A.; Zambrano, Eduardo

doi:10.1007/s12105-010-0174-6

Cited by 70 publications

(49 citation statements)

References 16 publications

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“…Variable positivity of NMC tumors has been noted for markers including CD99, FLI1, CD45 RO, NSE, CD34 (50%), vimentin, and focally, p16, CD56, CD138, TTF1, S-100, CD117, and PLAP. 6,11,[15][16][17][18][19][20][21] The antibody created to diagnose NMC with IHC is a rabbit monoclonal raised against amino acids 450 to 700 of the human NUT protein. 13 The IHC staining pattern demonstrates a diffuse (>90%), speckled nuclear staining in the malignant tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Retrospective analysis of nuclear protein in testis (NUT) midline carcinoma in the upper aerodigestive tract and mediastinum

Solomon¹,

Magliocca²,

Cohen³

et al. 2015

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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Section: Discussionmentioning

confidence: 99%

Retrospective analysis of nuclear protein in testis (NUT) midline carcinoma in the upper aerodigestive tract and mediastinum

Solomon¹,

Magliocca²,

Cohen³

et al. 2015

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

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“…NMC is named for its tendency to involve midline structures, but it doesn't always do so. It affects primarily the thorax (57 %, most often the mediastinum), and head and neck (35 %), but has involved the adrenal gland (unpublished observations), major salivary glands [11,12], pancreas [10], bladder [1], and lung [13].…”

Section: Clinico-pathologic Characteristicsmentioning

confidence: 99%

The Importance of Diagnosing NUT Midline Carcinoma

French

2013

Head and Neck Pathol

106

113

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NUT midline carcinoma (NMC) is an aggressive subset of squamous cell carcinoma, genetically defined by rearrangement of the NUT gene. The rearrangements most often take the form of BRD4-NUT fusions, and in a minority of cases, BRD3-NUT or NUT-variant fusions. The simple karyotypes of NMCs, in contrast to the complex ones of typical squamous cell carcinoma, suggest an alternate, genetic shortcut to squamous cancer. Although originally thought to be a disease of the mediastinum, NMC frequently (35 %) arises in the head and neck. Diagnosis is made simply by demonstration of nuclear immunoreactivity to NUT protein, and ancillary studies to characterize the fusion oncogene, though not required for diagnosis, are recommended. The prognosis is dismal, with a 6.7 month median survival, and treatment with conventional chemotherapeutic regimens is ineffective. The oncogenic mechanism of the dual bromodomains and the p300-binding portion of BRD4-NUT is to sequester p300 to localized regions of chromatin, leading to global transcriptional repression and blockade of differentiation. Two therapies which target this mechanism have emerged, including bromodomain inhibitors (BETi) and histone deacetylase inhibitors (HDACi), both of which induce differentiation and growth arrest of NMC cells, both in vitro and in vivo. BETi is available to adults with NMC through a phase I clinical trial, and clinical response to HDACi has been demonstrated in pediatric patients. The emergence of these promising targeted therapies gives hope that NMC may one day be effectively treated and provides a strong rationale for diagnostic testing for NMC.

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“…Subsequent publications have shown this tumor to not only have a broader age distribution that ranges from the first decade to the late eighth decade of life, but also a greater range of anatomic primaries with variations on the classic t(15;19) rearrangement [1,4]. Infradiafragmatic and non-midline structures have been involved, including medial thigh musculature, pancreas, liver, and bladder [3,5,12,14,15]. Pathologic evaluation of our patient's tumor showed a translocation involving three chromosomes resulting in a novel karyotype of 46XY, t(9;15;19; q34;q13;p13.1), and is only the second reported case with a three-way translocation [13].…”

Section: Discussionmentioning

confidence: 99%

NUT Midline Carcinoma: A Case Report with a Novel Translocation and Review of the Literature

Mills

Lanfranchi

Wein

et al. 2013

Head and Neck Pathol

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NUT midline carcinoma (NMC) is a rare, genetically defined, highly lethal undifferentiated carcinoma occurring in the midline location of the neck, head or mediastinum. We present the case of a 23 year-old otherwise healthy Chinese male immigrant who presented with complaints of sore throat and right sided neck mass. The initial treatment was for likely EBV infection with streptococcal superinfection. Although continued investigation was pursued shortly after initial presentation, the mass had enlarged and become necrotic with significant nodal involvement. The mass was diagnosed as an NMC tumor with a novel three-way translocation t(9;15;19; q34;q13; p13.1). Despite aggressive treatment, the patient's condition progressed rapidly and he died within 3 months of initial diagnosis. Standard therapeutic interventions have been ineffective in the treatment of NMC. Earlier diagnosis could allow characterization of the natural progression of this entity, and allow more time for intervention or development of novel therapies, potentially related to molecular targets. This continues to require a high index of suspicion and early imaging with cytogenetic and immunohistochemical confirmation.

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NUT Gene Rearrangement in a Poorly-differentiated Carcinoma of the Submandibular Gland

Cited by 70 publications

References 16 publications

Retrospective analysis of nuclear protein in testis (NUT) midline carcinoma in the upper aerodigestive tract and mediastinum

Retrospective analysis of nuclear protein in testis (NUT) midline carcinoma in the upper aerodigestive tract and mediastinum

The Importance of Diagnosing NUT Midline Carcinoma

NUT Midline Carcinoma: A Case Report with a Novel Translocation and Review of the Literature

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