Nuclear protein in testis (NUT) midline carcinoma with a novel three-way translocation (4;15;19)(q13;q14;p13.1)

Shatavi, S.; Fawole, Adewale; Haberichter, Kristle; Jaiyesimi, Ishmael; French, Christopher A.

doi:10.1016/j.pathol.2016.06.010

Cited by 9 publications

(6 citation statements)

References 11 publications

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“…The best OS for non-surgical patients of stage IV with primary pulmonary NUT carcinoma, with CD34-positive staining, was at least 100 weeks ( 61 , 92 ). The worst OS in stage IIIC non-surgical patients with CD34-negative staining was 2 months ( 93 ), while the best OS in stage IV non-surgical patients with CD34-negative staining was 148 weeks ( 52 , 61 ). Therefore, the published literatures have not found significant correlation between CD34 expression and the prognosis of patients with primary pulmonary NUT carcinoma, which needs more patients data for further evaluation.…”

Section: Targeting the Tumor Microenvironmentmentioning

confidence: 99%

Immunotherapy and Targeting the Tumor Microenvironment: Current Place and New Insights in Primary Pulmonary NUT Carcinoma

Shi

Zhang

et al. 2021

Front. Oncol.

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Primary pulmonary nuclear protein of testis carcinoma is a rare and highly aggressive malignant tumor. It accounts for approximately 0.22% of primary thoracic tumors and is little known, so it is often misdiagnosed as pulmonary squamous cell carcinoma. No effective treatment has been formed yet, and the prognosis is extremely poor. This review aims to summarize the etiology, pathogenesis, diagnosis, treatment, and prognosis of primary pulmonary nuclear protein of testis carcinoma in order to better recognize it and discuss the current and innovative strategies to overcome it. With the increasing importance of cancer immunotherapy and tumor microenvironment, the review also discusses whether immunotherapy and targeting the tumor microenvironment can improve the prognosis of primary pulmonary nuclear protein of testis carcinoma and possible treatment strategies. We reviewed and summarized the clinicopathological features of all patients with primary pulmonary nuclear protein of testis carcinoma who received immunotherapy, including initial misdiagnosis, disease stage, immunohistochemical markers related to tumor neovascularization, and biomarkers related to immunotherapy, such as PD-L1 (programmed death-ligand 1) and TMB (tumor mutational burden). In the meanwhile, we summarized and analyzed the progression-free survival (PFS) and the overall survival (OS) of patients with primary pulmonary nuclear protein of testis carcinoma treated with PD-1 (programmed cell death protein 1)/PD-L1 inhibitors and explored potential population that may benefit from immunotherapy. To the best of our knowledge, this is the first review on the exploration of the tumor microenvironment and immunotherapy effectiveness in primary pulmonary nuclear protein of testis carcinoma.

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Section: Targeting the Tumor Microenvironmentmentioning

confidence: 99%

Immunotherapy and Targeting the Tumor Microenvironment: Current Place and New Insights in Primary Pulmonary NUT Carcinoma

Shi

Zhang

et al. 2021

Front. Oncol.

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“…Shiota et al found that NUT is expressed in post-meiotic spermatogenic germ cells, and it can recruit p300 and/or CBP and enhance histone H4K5 and H4K8 acetylation, leading to the histone-to-protamine replacement (16). In the rearrangement gene expression of NC, the NUTM1 (NUT) gene usually uses bromodomaincontaining protein 4 (BRD4) as a fusion partner, sometimes uses BRD3, and, in a few cases, uses NSD3 (17,18 (20). A new type of NUT fusion partner MGA has also been reported (21,22), but this pathology is ultimately classified as a sarcoma; MXD4, a novel partner, is reported recently (21,23).…”

Section: Multiple Gene Rearrangementmentioning

confidence: 99%

Advances in the pathogenesis and treatment of nut carcinoma: a narrative review

Wang¹,

Li²,

Tong³

et al. 2020

Transl Cancer Res TCR

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NUT carcinoma (NC) is a rare, highly invasive and fatal tumor and often misdiagnosed. It typically arises from the mediastinum and midline organs and has complicated pathogenesis and poor outcome. Genetically, its pathogenesis is related to a chromosomal rearrangement involving the NUTM1 gene. In most cases, the main oncoprotein is BRD4-NUT with a translocation between NUTM1 and BRD4 genes, but in a few cases, the oncoprotein is BRD3-NUT, or NSD3-NUT. Studies have shown that the histone hyperacetylation and BRD4 hyperphosphorylation may lead to the activation of cancer circuits.Abnormal production of microRNA, inactivation of tumor suppressor genes and abnormal activation of several signaling pathways are proposed as potential mechanisms underlying the pathogenesis of NC.Currently, there is no consensus on its standard treatment for NC. Extent of surgical resection with negative margins, initial radiotherapy and part of chemotherapy regimens may significantly associated with the improvement of progression-free survival (PFS) rate and overall survival (OS) rate. Some bromodomain and extraterminal inhibitors (BETis) have shown encouraging results in the clinical trials on NC, but delayed drug resistance is still an important issue that needs to be resolved. Histone deacetylase inhibitors are also found to possess the potential in the treatment of NC. Herein, we summarize recent advances in the pathogenesis and treatment of NC.

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“…In the remaining cases, NUT is fused with BRD3 (25%) or to unidentified genes (5%). In recent reports, a NSD3-(nuclear receptor binding SET domain 3) NUT fusion was also identified, and a novel three-way translocation involving chromosomes 9, 15, and 19 [10] [11] [12]. The BRD-NUT fusion proteins appear to contribute to carcinogenesis by interacting with chromatin, triggering aberrant histone acetylation, and blocking cellular differentiation.…”

Section: Introductionmentioning

confidence: 99%

Prolonged Disease Stabilization and Tolerability in a Nuclear Protein in Testis Midline Carcinoma Patient Treated with Dual Histone Deacetylase and Phosphoinositide 3-Kinase Inhibitor CUDC-907

Münster¹,

Wu²,

McMahon³

et al. 2018

CRCM

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Introduction: Nuclear protein in testis midline carcinoma (NMC) is a rare and extremely aggressive carcinoma (median survival < 7 months) with no effective treatment options. CUDC-907 is a novel small molecule inhibitor of histone deacetylase (HDAC) and phosphoinositide 3-kinase (PI3K) enzymes currently being investigated in multiple tumor types, including NMC. Case Report: A 61-year old female NMC patient enrolled on study CUDC-907-102 (NCT02307240) after rapidly progressing through two prior treatments. The patient's assessable sites of disease consisted of right pleural effusion, right hilar soft tissue, and segment IV liver. Treatment was well tolerated with toxicities primarily consisting of manageable diarrhea and thrombocytopenia. The patient remains on active treatment after more than 32 months of stable disease. Discussion: Dysregulation of MYC in NMC is believed to play a central role in pathogenesis. CUDC-907 has demonstrated potent suppression of MYC expression and anti-tumor activity in preclinical NMC models, providing a mechanistic rationale for the prolonged disease stabilization observed here. The treatment of additional NMC patients with CUDC-907 is needed to further evaluate this promising report. Conclusion: This case demonstrates a rare success in the treatment of a devastating disease using only a novel small molecule, warranting further investigation of CUDC-907 in NMC.

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Nuclear protein in testis (NUT) midline carcinoma with a novel three-way translocation (4;15;19)(q13;q14;p13.1)

Cited by 9 publications

References 11 publications

Immunotherapy and Targeting the Tumor Microenvironment: Current Place and New Insights in Primary Pulmonary NUT Carcinoma

Immunotherapy and Targeting the Tumor Microenvironment: Current Place and New Insights in Primary Pulmonary NUT Carcinoma

Advances in the pathogenesis and treatment of nut carcinoma: a narrative review

Prolonged Disease Stabilization and Tolerability in a Nuclear Protein in Testis Midline Carcinoma Patient Treated with Dual Histone Deacetylase and Phosphoinositide 3-Kinase Inhibitor CUDC-907

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