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NUT midline carcinoma

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https://www.readbyqxmd.com/read/29040054/pediatric-nut-midline-carcinoma-therapeutic-success-employing-a-sarcoma-based-multimodal-approach
#1
Simone Storck, Alyssa L Kennedy, Karen J Marcus, Lisa Teot, Jennifer Vaughn, Astrid K Gnekow, Bruno Märkl, Ivo Leuschner, Steven G DuBois, Christopher A French, Michael C Frühwald
A subset of poorly differentiated squamous cell carcinomas, NUT midline carcinomas (NMC) are characterized by a translocation t(15;19)(q13;p13) [ 1 ]. The prognosis is generally dismal [ 2 ] and therapeutic success has been limited to exceptional cases [ 3 ]. We present two cases of pediatric NMC from two different institutions treated according to a multimodal sarcoma approach involving surgery, chemotherapy, and focal radiotherapy. One patient has remained in complete continuous remission for over 6 years, while the other is in CR in early follow-up off therapy...
October 17, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/28967088/uncommon-somatic-mutations-in-metastatic-nut-midline-carcinoma
#2
Stefano Cavalieri, Anastasios Stathis, Alessandra Fabbri, Angelica Sonzogni, Federica Perrone, Elena Tamborini, Giuseppe Pelosi, Filippo de Braud, Marco Platania
INTRODUCTION: NUT midline carcinoma (NMC) is a rare and aggressive epithelial cancer arising from median organs. It is driven by chromosomal translocation t(15;19) involving the rearrangement of NUT (nuclear protein in testis) and BRD4 (bromodomain 4) genes leading to fusion oncoprotein BRD4-NUT. CASE PRESENTATION: We report the case of a woman who was previously treated with induction chemotherapy, surgery, radiotherapy and adjuvant trastuzumab for HER-2 positive invasive ductal carcinoma of the breast...
September 25, 2017: Tumori
https://www.readbyqxmd.com/read/28948459/nut-midline-carcinoma-a-series-of-five-cases-including-one-with-unusual-clinical-course
#3
Aanchal Kakkar, Vijay Mariadas Antony, David Victor Kumar Irugu, Narayan Adhikari, Deepali Jain
NUT midline carcinomas (NMCs) are rare, poorly differentiated tumors with aggressive biological behavior and a characteristic molecular signature. Availability of NUT antibody has facilitated diagnosis of NMC without molecular testing. We report a series of head and neck NMCs diagnosed using NUT IHC at our institute, including one case with an unusual course. Immunohistochemistry for NUT was performed in nasal and sinonasal tumors with diagnoses of undifferentiated carcinoma, poorly differentiated squamous cell carcinoma and malignant neoplasm, not otherwise specified, to identify cases of NMC...
September 25, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/28930680/systematic-kinase-inhibitor-profiling-identifies-cdk9-as-a-synthetic-lethal-target-in-nut-midline-carcinoma
#4
Johannes Brägelmann, Marcel A Dammert, Felix Dietlein, Johannes M Heuckmann, Axel Choidas, Stefanie Böhm, André Richters, Debjit Basu, Verena Tischler, Carina Lorenz, Peter Habenberger, Zhizhou Fang, Sandra Ortiz-Cuaran, Frauke Leenders, Jan Eickhoff, Uwe Koch, Matthäus Getlik, Martin Termathe, Muhammad Sallouh, Zoltán Greff, Zoltán Varga, Hyatt Balke-Want, Christopher A French, Martin Peifer, H Christian Reinhardt, László Örfi, György Kéri, Sascha Ansén, Lukas C Heukamp, Reinhard Büttner, Daniel Rauh, Bert M Klebl, Roman K Thomas, Martin L Sos
Kinase inhibitors represent the backbone of targeted cancer therapy, yet only a limited number of oncogenic drivers are directly druggable. By interrogating the activity of 1,505 kinase inhibitors, we found that BRD4-NUT-rearranged NUT midline carcinoma (NMC) cells are specifically killed by CDK9 inhibition (CDK9i) and depend on CDK9 and Cyclin-T1 expression. We show that CDK9i leads to robust induction of apoptosis and of markers of DNA damage response in NMC cells. While both CDK9i and bromodomain inhibition over time result in reduced Myc protein expression, only bromodomain inhibition induces cell differentiation and a p21-induced cell-cycle arrest in these cells...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28837236/renal-nut-carcinoma-a-case-report
#5
Deepika Sirohi, Karuna Garg, Jeffry P Simko, James P Grenert
Nuclear protein in testis (NUT)-midline carcinomas were first described more than two decades ago with characteristic reciprocal translocations involving BRD4 on chromosomes 15 and NUTM1 on chromosome 19 (1). Over the years, these tumors have been reported in non-midline locations as well as outside of the upper aerodigestive tract and mediastinum. We recently encountered a renal NUT carcinoma (NC) diagnosed next generation sequencing (NGS) that is reported here. This article is protected by copyright. All rights reserved...
August 24, 2017: Histopathology
https://www.readbyqxmd.com/read/28797547/nut-midline-carcinoma-causing-critical-stenosis-of-the-coronary-arteries-ct-demonstration
#6
Luis Gorospe, Ana María Ayala-Carbonero, Frank Eric Farfán-Leal, Gemma María Muñoz-Molina, María Eugenia Olmedo-García, Ana Gómez-Rueda, Pilar Garrido-López
No abstract text is available yet for this article.
August 7, 2017: Surgery
https://www.readbyqxmd.com/read/28729764/deciphering-the-role-of-micrornas-in-brd4-nut-fusion-gene-induced-nut-midline-carcinoma
#7
Ekta Pathak, Bhavya, Divya Mishra, Neelam Atri, Rajeev Mishra
NUT midline carcinoma (NMC) is a very aggressive and lethal type of squamous epithelial cell cancer caused due to fusion of BRD4 and NUT genes. The gene fusion results into a new fusion protein that promotes oncogenesis. The detailed molecular mechanisms underlying the NMC are still not clear and new findings are urgently required to complement the current efforts. Abnormal microRNAs (miRNA) expression promotes tumour formation by modulating the functional expression of critical genes other than the parent genes involved in tumour cell proliferation or survival...
2017: Bioinformation
https://www.readbyqxmd.com/read/28670187/nuclear-protein-in-testis-midline-carcinoma-presenting-in-an-infant-as-a-pericardial-mass-with-staging-by-18-f-fluorodeoxyglucose-positron-emission-tomography-computed-tomography
#8
Crystal Perkins, Darko Pucar, Colleen H McDonough, Hadyn T Williams
Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare, aggressive, lethal, epithelioid, poorly differentiated cancer first described in Japan in 1991, unique in that is defined genetically rather than by histological tissue of origin. It usually arises in the body midline and presents as a mass with metastasis. An infant presenting with pneumonia was found to have a pericardial mass, NMC resected, and subsequent staging positron emission tomography (PET) showing residual mediastinal tumor and midline abdominal metastases...
July 2017: World Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28643357/nut-carcinoma-in-children-and-adults-a-multicenter-retrospective-study
#9
MULTICENTER STUDY
Lauriane Lemelle, Gaëlle Pierron, Paul Fréneaux, Sophie Huybrechts, Alexandra Spiegel, Dominique Plantaz, Morbize Julieron, Sophie Dumoucel, Antoine Italiano, Fréderic Millot, Christophe Le Tourneau, Guy Leverger, Pascal Chastagner, Matthieu Carton, Daniel Orbach
BACKGROUND: Nuclear protein of the testis (NUT) carcinoma (formerly NUT midline carcinoma) is an aggressive tumor defined by the presence of NUT rearrangement with a poor prognosis. This rare cancer is underdiagnosed and poorly treated. OBJECTIVE: The primary objective of this study was to describe the clinical, radiologic, and biological features of NUT carcinoma. The secondary objective was to describe the various treatments and assess their efficacy. METHODS: This retrospective multicenter study was based on review of the medical records of children and adults with NUT carcinoma with specific rearrangement or positive anti-NUT nuclear staining (>50%)...
December 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28640941/phox2b-reliably-distinguishes-neuroblastoma-among-small-round-blue-cell-tumours
#10
Yin P Hung, John P Lee, Andrew M Bellizzi, Jason L Hornick
AIMS: Neuroblastoma shows considerable histological overlap with other small round blue cell tumours. PHOX2B, a transcription factor that is essential for autonomic nervous system development, has been reported as an immunohistochemical marker for neuroblastoma. The aim of this study was to validate the specificity and diagnostic utility of PHOX2B for peripheral neuroblastic tumours. METHODS AND RESULTS: We evaluated 240 cases (133 in whole-tissue sections; 107 in tissue microarrays), including 76 peripheral neuroblastic tumours (median age 2 years; including four adults) and 164 other tumours: 44 Wilms tumours; 20 Ewing sarcomas; 10 each of CIC-rearranged round cell sarcomas, poorly differentiated synovial sarcomas, lymphoblastic lymphomas, alveolar rhabdomyosarcomas, embryonal rhabdomyosarcomas, mesenchymal chondrosarcomas, Merkel cell carcinomas, olfactory neuroblastomas, and melanomas; and five each of NUT midline carcinomas and desmoplastic small round cell tumours...
June 22, 2017: Histopathology
https://www.readbyqxmd.com/read/28630312/uncovering-brd4-hyperphosphorylation-associated-with-cellular-transformation-in-nut-midline-carcinoma
#11
Ranran Wang, Xing-Jun Cao, Katarzyna Kulej, Wei Liu, Tongcui Ma, Margo MacDonald, Cheng-Ming Chiang, Benjamin A Garcia, Jianxin You
The epigenetic reader BRD4 plays a vital role in transcriptional regulation, cellular growth control, and cell-cycle progression. Dysregulation of BRD4 function has been implicated in the pathogenesis of a wide range of cancers. However, how BRD4 is regulated to maintain its normal function in healthy cells and how alteration of this process leads to cancer remain poorly understood. In this study, we discovered that BRD4 is hyperphosphorylated in NUT midline carcinoma and identified CDK9 as a potential kinase mediating BRD4 hyperphosphorylation...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28525743/bromodomain-protein-brd4-is-a-transcriptional-repressor-of-autophagy-and-lysosomal-function
#12
Jun-Ichi Sakamaki, Simon Wilkinson, Marcel Hahn, Nilgun Tasdemir, Jim O'Prey, William Clark, Ann Hedley, Colin Nixon, Jaclyn S Long, Maria New, Tim Van Acker, Sharon A Tooze, Scott W Lowe, Ivan Dikic, Kevin M Ryan
Autophagy is a membrane-trafficking process that directs degradation of cytoplasmic material in lysosomes. The process promotes cellular fidelity, and while the core machinery of autophagy is known, the mechanisms that promote and sustain autophagy are less well defined. Here we report that the epigenetic reader BRD4 and the methyltransferase G9a repress a TFEB/TFE3/MITF-independent transcriptional program that promotes autophagy and lysosome biogenesis. We show that BRD4 knockdown induces autophagy in vitro and in vivo in response to some, but not all, situations...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28484033/ectopic-protein-interactions-within-brd4-chromatin-complexes-drive-oncogenic-megadomain-formation-in-nut-midline-carcinoma
#13
Artyom A Alekseyenko, Erica M Walsh, Barry M Zee, Tibor Pakozdi, Peter Hsi, Madeleine E Lemieux, Paola Dal Cin, Tan A Ince, Peter V Kharchenko, Mitzi I Kuroda, Christopher A French
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...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28441376/nut-midline-carcinoma-a-rare-malignancy
#14
Sameer Al Diffalha, Nidal Al Aukla, Saleh Hasan, Shohreh Dickinson, Farah Khalil
Nuclear protein of the testis (NUT) midline carcinoma can present in the head, neck, and mediastinum. In general, it presents in young adult men and has a poor prognosis. We report on a case of NUT midline carcinoma of the mediastinum in a man 27 years of age without any prior malignancy. Due to the location of the tumor, mediastinal lymphoma and germ cell tumor were initially considered; however, immunohistochemistry was performed using NUT antibody that revealed it to be NUT midline carcinoma. Although guidelines exist for squamous cell carcinoma of the head, neck, and mediastinum, no such specific guidelines are available for NUT midline carcinoma, which looks morphologically similar to squamous cell carcinoma but behaves more aggressively and carries a poor prognosis...
April 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28426098/targeting-chromatin-defects-in-selected-solid-tumors-based-on-oncogene-addiction-synthetic-lethality-and-epigenetic-antagonism
#15
D Morel, G Almouzni, J-C Soria, S Postel-Vinay
Background: Although the role of epigenetic abnormalities has been studied for several years in cancer genesis and development, epigenetic-targeting drugs have historically failed to demonstrate efficacy in solid malignancies. However, successful targeting of chromatin remodeling deficiencies, histone writers and histone reader alterations has been achieved very recently using biomarker-driven and mechanism-based approaches. Epigenetic targeting is now one of the most active areas in drug development and could represent novel therapeutic opportunity for up to 25% of all solid tumors...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28407756/alpha-fetoprotein-elevation-in-nut-midline-carcinoma-a-case-report
#16
Lorenzo D'Ambrosio, Erica Palesandro, Marina Moretti, Giuseppe Pelosi, Alessandra Fabbri, Fabrizio Carnevale Schianca, Massimo Aglietta, Giovanni Grignani
BACKGROUND: Nuclear protein in testis (NUT) midline carcinoma is a rarely diagnosed and potentially under-recognized type of squamous carcinoma that is considered one of the most aggressive human solid tumors. Alpha-fetoprotein elevation has been associated with chronic liver diseases and a limited number of cancers. In particular, in presence of a mediastinal mass in a young man, alpha-fetoprotein elevation is considered nearly pathognomonic of a non-seminoma germ-cell tumor. CASE PRESENTATION: A 22-year old man without any comorbidity was diagnosed with a large mediastinal mass with skeletal and lymph node metastases...
April 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28349372/nut-midline-carcinoma-of-the-sublingual-gland-clinical-presentation-and-review
#17
Nolan B Seim, Ramez H W Philips, Lynn Schoenfield, Theodoros N Teknos, James W Rocco, Amit Agrawal, Enver Ozer, Ricardo L Carrau, Stephen Y Kang, Matthew O Old
NUT midline carcinoma (NMC) is a rare and aggressive disease encountered in the midline of the head and neck or mediastinum. Due to its sparse incidence and subtle pathologic features, we aim to increase knowledge and awareness for this pathologic entity. We present an exemplary case of a young, healthy male presenting with oral cavity pain and cervical lymphadenopathy. This patient was initially diagnosed with an unspecified, highly aggressive sublingual gland malignancy and underwent locoregional resection with free flap reconstruction however suffered a rapid local recurrence and widely extensive metastasis within just 1 month...
March 27, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/28203693/complex-chromosomal-rearrangements-by-single-catastrophic-pathogenesis-in-nut-midline-carcinoma
#18
J-K Lee, S Louzada, Y An, S Y Kim, S Kim, J Youk, S Park, S H Koo, B Keam, Y K Jeon, J-L Ku, F Yang, T M Kim, Y S Ju
Background: Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare aggressive malignancy often occurring in the tissues of midline anatomical structures. Except for the pathognomonic BRD3/4-NUT rearrangement, the comprehensive landscape of genomic alterations in NMCs has been unexplored. Patients and methods: We investigated three NMC cases, including two newly diagnosed NMC patients in Seoul National University Hospital, and a previously reported cell line (Ty-82)...
April 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28176137/smarca4-deficient-sinonasal-carcinoma
#19
Abbas Agaimy, Wilko Weichert
The term "sinonasal undifferentiated carcinoma (SNUC)" has been coined in 1986 for a highly aggressive sinonasal tract epithelial neoplasm showing distinctive morphology, but lacking any specific line of differentiation. Recent developments resulted in a dynamic splitting of new entities traditionally included in the spectrum of SNUC. Sinonasal NUT-midline carcinoma, adamantinoma-like Ewing family tumors and most recently, SMARCB1(INI1)-deficient sinonasal carcinoma are the main entities defined by specific genetic aberrations...
February 7, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/27980108/dual-hdac-and-pi3k-inhibitor-cudc-907-downregulates-myc-and-suppresses-growth-of-myc-dependent-cancers
#20
Kaiming Sun, Ruzanna Atoyan, Mylissa A Borek, Steven Dellarocca, Maria Elena S Samson, Anna W Ma, Guang-Xin Xu, Troy Patterson, David P Tuck, Jaye L Viner, Ali Fattaey, Jing Wang
Upregulation of MYC is a common driver event in human cancers, and some tumors depend on MYC to maintain transcriptional programs that promote cell growth and proliferation. Preclinical studies have suggested that individually targeting upstream regulators of MYC, such as histone deacetylases (HDAC) and phosphoinositide 3-kinases (PI3K), can reduce MYC protein levels and suppress the growth of MYC-driven cancers. Synergy between HDAC and PI3K inhibition in inducing cancer cell death has also been reported, but the involvement of MYC regulation is unclear...
February 2017: Molecular Cancer Therapeutics
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