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Article: DYRK3 contributes to differentiation and hypoxic control in neuroblastoma

Ivanova, Ekaterina / Sharma, Shrey Dharamvir / Brichkina, Anna / Pfefferle, Petra / Keber, Ursula / Pagenstecher, Axel / Lauth, Matthias

Biochemical and biophysical research communications. 2021 Aug. 27, v. 567

2021

Abstract: Neuroblastoma (NB), a pediatric cancer of the peripheral sympathetic nervous system, represents the most frequent solid malignancy in infants. Treatment of high-risk patients is still challenging and, depending on the genetic make-up and involved risk ... ...

Abstract	Neuroblastoma (NB), a pediatric cancer of the peripheral sympathetic nervous system, represents the most frequent solid malignancy in infants. Treatment of high-risk patients is still challenging and, depending on the genetic make-up and involved risk factors, the 5-year survival rate can drop to only 30%. Here, we found that the expression of the Dual Specificity Tyrosine Phosphorylation Regulated Kinase 3 (DYRK3) is increased in NB and is associated with decreased survival in NB patients. We further identified DYRK3 as a cytoplasmic kinase in NB cells and found that its levels are increased by hypoxic conditions. Further mechanistic studies revealed that DYRK3 acts as a negative regulator of HIF-driven transcriptional responses, suggesting that it functions in a negative feedback loop controlling the hypoxic response. Moreover, DYRK3 negatively impacted on NB cell differentiation, proposing an oncogenic role of this kinase in the etiology of NB. In summary, we describe novel functions of the DYRK3 kinase in NB, which will help to further improve the understanding of this disease eventually leading to the design of improved therapeutic concepts.
Keywords	cell differentiation ; etiology ; phosphorylation ; research ; survival rate ; sympathetic nervous system ; therapeutics ; transcription (genetics) ; tyrosine
Language	English
Dates of publication	2021-0827
Size	p. 215-221.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2021.06.053
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Amyopathic and anti-TIF1 gamma-positive dermatomyositis: analysis of a monocentric cohort and proposal to update diagnostic criteria.

Didona, Dario / Juratli, Hazem A / Scarsella, Luca / Keber, Ursula / Eming, Rüdiger / Hertl, Michael

European journal of dermatology : EJD

2020 Volume 30, Issue 3, Page(s) 279–288

Abstract: Dermatomyositis (DM) is a group of autoimmune diseases characterized by a variable degree of skin symptoms and myopathy. An amyopathic form of DM (ADM) has been described, and more recently, an anti-TIF-1 gamma-positive subtype, characterized by ... ...

Abstract	Dermatomyositis (DM) is a group of autoimmune diseases characterized by a variable degree of skin symptoms and myopathy. An amyopathic form of DM (ADM) has been described, and more recently, an anti-TIF-1 gamma-positive subtype, characterized by poikiloderma and associated with a relatively high risk of cancer. To characterise a cohort of DM patients. A cohort of 29 DM patients was followed between January 2004 and March 2019, and investigated for clinical characteristics, pathological features based on electromyography and MRI, laboratory data, and auto-antibody profile. Based on the investigations, DM was shown to be heterogeneous. However, we identified a subgroup of anti-TIF-1 gamma-positive patients who all shared heliotrope erythema. Furthermore, we observed a positive correlation between serum glutamicoxaloacetic transaminase (GOT) and creatine kinase (CK) concentrations in patients with anti-TIF-1 gamma antibodies, which is not found in patients with anti-MDA-5 antibodies. Based on the findings of this study, we propose an update of the Sontheimer et al. diagnostic criteria to improve the sensitivity of diagnosis for ADM. In addition, we describe a significant association between serum GOT and CK levels in DM patients with anti-TIF-1 gamma antibodies, and further highlight the significance of heliotrope rash as a clinical hallmark for this particular subset of patients.
MeSH term(s)	Alanine Transaminase/blood ; Antibodies, Antinuclear/blood ; Aspartate Aminotransferases/blood ; Biopsy ; Creatine Kinase/blood ; Dermatomyositis/complications ; Dermatomyositis/diagnosis ; Dermatomyositis/pathology ; Dermatomyositis/physiopathology ; Electromyography ; Erythema/etiology ; Female ; Humans ; Interferon-Induced Helicase, IFIH1/immunology ; L-Lactate Dehydrogenase/blood ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Muscle, Skeletal/pathology ; Paraneoplastic Syndromes/diagnosis ; Photosensitivity Disorders/etiology ; Skin/pathology ; Transcription Factors/immunology
Chemical Substances	Antibodies, Antinuclear ; TRIM33 protein, human ; Transcription Factors ; L-Lactate Dehydrogenase (EC 1.1.1.27) ; Aspartate Aminotransferases (EC 2.6.1.1) ; Alanine Transaminase (EC 2.6.1.2) ; Creatine Kinase (EC 2.7.3.2) ; IFIH1 protein, human (EC 3.6.1.-) ; Interferon-Induced Helicase, IFIH1 (EC 3.6.4.13)
Language	English
Publishing date	2020-07-14
Publishing country	France
Document type	Journal Article
ZDB-ID	1128666-0
ISSN	1952-4013 ; 1167-1122
ISSN (online)	1952-4013
ISSN	1167-1122
DOI	10.1684/ejd.2020.3766
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Zs.A 3484: Show issues

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Article ; Online: DYRK3 contributes to differentiation and hypoxic control in neuroblastoma.

Ivanova, Ekaterina / Sharma, Shrey Dharamvir / Brichkina, Anna / Pfefferle, Petra / Keber, Ursula / Pagenstecher, Axel / Lauth, Matthias

Biochemical and biophysical research communications

2021 Volume 567, Page(s) 215–221

Abstract	Neuroblastoma (NB), a pediatric cancer of the peripheral sympathetic nervous system, represents the most frequent solid malignancy in infants. Treatment of high-risk patients is still challenging and, depending on the genetic make-up and involved risk factors, the 5-year survival rate can drop to only 30%. Here, we found that the expression of the Dual Specificity Tyrosine Phosphorylation Regulated Kinase 3 (DYRK3) is increased in NB and is associated with decreased survival in NB patients. We further identified DYRK3 as a cytoplasmic kinase in NB cells and found that its levels are increased by hypoxic conditions. Further mechanistic studies revealed that DYRK3 acts as a negative regulator of HIF-driven transcriptional responses, suggesting that it functions in a negative feedback loop controlling the hypoxic response. Moreover, DYRK3 negatively impacted on NB cell differentiation, proposing an oncogenic role of this kinase in the etiology of NB. In summary, we describe novel functions of the DYRK3 kinase in NB, which will help to further improve the understanding of this disease eventually leading to the design of improved therapeutic concepts.
MeSH term(s)	Animals ; Cell Line, Tumor ; Female ; Humans ; Mice ; Neuroblastoma/metabolism ; Neuroblastoma/pathology ; Protein-Serine-Threonine Kinases/analysis ; Protein-Serine-Threonine Kinases/metabolism ; Protein-Tyrosine Kinases/analysis ; Protein-Tyrosine Kinases/metabolism ; Tumor Hypoxia
Chemical Substances	DYRK3 protein, mouse (EC 2.7.-) ; DYRK3 protein, human (EC 2.7.1.11) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2021-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2021.06.053
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Article ; Online: Brain-to-gut trafficking of alpha-synuclein by CD11c

McFleder, Rhonda L / Makhotkina, Anastasiia / Groh, Janos / Keber, Ursula / Imdahl, Fabian / Peña Mosca, Josefina / Peteranderl, Alina / Wu, Jingjing / Tabuchi, Sawako / Hoffmann, Jan / Karl, Ann-Kathrin / Pagenstecher, Axel / Vogel, Jörg / Beilhack, Andreas / Koprich, James B / Brotchie, Jonathan M / Saliba, Antoine-Emmanuel / Volkmann, Jens / Ip, Chi Wang

Nature communications

2023 Volume 14, Issue 1, Page(s) 7529

Abstract: Inflammation in the brain and gut is a critical component of several neurological diseases, such as Parkinson's disease (PD). One trigger of the immune system in PD is aggregation of the pre-synaptic protein, α-synuclein (αSyn). Understanding the ... ...

Abstract	Inflammation in the brain and gut is a critical component of several neurological diseases, such as Parkinson's disease (PD). One trigger of the immune system in PD is aggregation of the pre-synaptic protein, α-synuclein (αSyn). Understanding the mechanism of propagation of αSyn aggregates is essential to developing disease-modifying therapeutics. Using a brain-first mouse model of PD, we demonstrate αSyn trafficking from the brain to the ileum of male mice. Immunohistochemistry revealed that the ileal αSyn aggregations are contained within CD11c
MeSH term(s)	Male ; Animals ; Mice ; alpha-Synuclein/genetics ; Parkinson Disease/genetics ; Brain ; Disease Models, Animal ; Ileum
Chemical Substances	alpha-Synuclein
Language	English
Publishing date	2023-11-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-43224-z
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Article ; Online: Homozygous TBC1 domain-containing kinase (TBCK) mutation causes a novel lysosomal storage disease - a new type of neuronal ceroid lipofuscinosis (CLN15)?

Beck-Wödl, Stefanie / Harzer, Klaus / Sturm, Marc / Buchert, Rebecca / Rieß, Olaf / Mennel, Hans-Dieter / Latta, Elisabeth / Pagenstecher, Axel / Keber, Ursula

Acta neuropathologica communications

2018 Volume 6, Issue 1, Page(s) 145

Abstract: Homozygous mutation of TBC1 domain-containing kinase (TBCK) is the cause of a very recently defined severe childhood disorder, which is characterized by severe hypotonia, global developmental delay, intellectual disability, epilepsy, characteristic ... ...

Abstract	Homozygous mutation of TBC1 domain-containing kinase (TBCK) is the cause of a very recently defined severe childhood disorder, which is characterized by severe hypotonia, global developmental delay, intellectual disability, epilepsy, characteristic facies and premature death. The link between TBCK loss of function and symptoms in patients with TBCK deficiency disorder (TBCK-DD) remains elusive. Here we demonstrate for the first time the histopathological characteristics of TBCK deficiency consisting of 1) a widespread and massive accumulation of lipofuscin storage material in neurons of the central nervous system without notable neuronal degeneration, 2) storage deposits in few astrocytes, 3) carbohydrate-rich deposits in brain, spleen and liver and 4) vacuolated lymphocytes. Biochemical examinations ruled out more than 20 known lysosomal storage diseases. These investigations strikingly uncover TBCK-DD as a novel type of lysosomal storage disease which is characterized by different storage products rather than one specific type of accumulated material. Due to the clear predominance of intraneuronal lipofuscin storage material and the characteristic clinical presentation we propose to classify this disease as a new subtype of neuronal ceroid lipofuscinosis (CLN15). Our results and previous reports suggest an autophagosomal-lysosomal dysfunction caused by enhanced mTORC1-mediated autophagosome formation and reduced Rab-mediated autophagosome-lysosome fusion, thus disclosing potential novel targets for therapeutic approaches in TBCK-DD.
MeSH term(s)	Antigens, CD/metabolism ; Child ; DNA Mutational Analysis ; Electroencephalography ; Female ; Glial Fibrillary Acidic Protein/metabolism ; Homozygote ; Humans ; Lipofuscin/metabolism ; Lymphocytes/metabolism ; Lymphocytes/pathology ; Lymphocytes/ultrastructure ; Lysosomal Storage Diseases/genetics ; Lysosomal Storage Diseases/metabolism ; Lysosomal Storage Diseases/pathology ; Lysosomes/metabolism ; Lysosomes/pathology ; Mutation/genetics ; Nervous System/metabolism ; Nervous System/pathology ; Nervous System/ultrastructure ; Protein-Serine-Threonine Kinases/genetics ; Siblings ; Spinal Cord/metabolism ; Spinal Cord/pathology ; Spinal Cord/ultrastructure
Chemical Substances	Antigens, CD ; Glial Fibrillary Acidic Protein ; Lipofuscin ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; TBCK protein, human (EC 2.7.11.1)
Language	English
Publishing date	2018-12-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2715589-4
ISSN	2051-5960 ; 2051-5960
ISSN (online)	2051-5960
ISSN	2051-5960
DOI	10.1186/s40478-018-0646-6
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Article ; Online: Neurodegeneration by α-synuclein-specific T cells in AAV-A53T-α-synuclein Parkinson's disease mice.

Brain, behavior, and immunity

2022 Volume 101, Page(s) 194–210

Abstract: Background: Antigen-specific neuroinflammation and neurodegeneration are characteristic for neuroimmunological diseases. In Parkinson's disease (PD) pathogenesis, α-synuclein is a known culprit. Evidence for α-synuclein-specific T cell responses was ... ...

Abstract	Background: Antigen-specific neuroinflammation and neurodegeneration are characteristic for neuroimmunological diseases. In Parkinson's disease (PD) pathogenesis, α-synuclein is a known culprit. Evidence for α-synuclein-specific T cell responses was recently obtained in PD. Still, a causative link between these α-synuclein responses and dopaminergic neurodegeneration had been lacking. We thus addressed the functional relevance of α-synuclein-specific immune responses in PD in a mouse model. Methods: We utilized a mouse model of PD in which an Adeno-associated Vector 1/2 serotype (AAV1/2) expressing human mutated A53T-α-Synuclein was stereotactically injected into the substantia nigra (SN) of either wildtype C57BL/6 or Recombination-activating gene 1 (RAG1) Results: AAV-based overexpression of pathogenic human A53T-α-synuclein in dopaminergic neurons of the SN stimulated T cell infiltration. RNA-sequencing of immune cells from PD mouse brains confirmed a pro-inflammatory gene profile. T cell responses were directed against A53T-α-synuclein-peptides in the vicinity of position 53 (68-78) and surrounding the pathogenically relevant S129 (120-134). T cells were required for α-synuclein-induced neurodegeneration in vivo and in vitro, while B cell deficiency did not protect from dopaminergic neurodegeneration. Conclusions: Using T cell and/or B cell deficient mice and a newly developed A53T-α-synuclein-expressing neuronal cell culture/immune cell assay, we confirmed in vivo and in vitro that pathogenic α-synuclein peptide-specific T cell responses can cause dopaminergic neurodegeneration and thereby contribute to PD-like pathology.
MeSH term(s)	Animals ; Disease Models, Animal ; Dopamine ; Dopaminergic Neurons/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Parkinson Disease/pathology ; RNA ; Substantia Nigra/metabolism ; T-Lymphocytes/metabolism ; alpha-Synuclein/metabolism
Chemical Substances	alpha-Synuclein ; RNA (63231-63-0) ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2022-01-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2022.01.007
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Zs.A 2276: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 327: Show issues

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Book ; Online ; Thesis: Die Rolle von striatalen Tyrosinhydroxylase-positiven Neuronen bei L-DOPA-induzierten Dyskinesien der Maus

Keber, Ursula Johanna [Verfasser] / Depboylu, Candan [Akademischer Betreuer]

2014

Author's details	Ursula Johanna Keber. Betreuer: Candan Depboylu
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Publisher	Philipps-Universität Marburg
Publishing place	Marburg
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Immune checkpoint inhibitor-associated CNS autoimmune disorder (ICICAD) following nivolumab treatment: A new entity of drug-induced autoimmune encephalitis?

Strik, Herwig / Keber, Ursula / Hammoud, Wasim Alhaj / Riera-Knorrenschild, Jorge / Carl, Barbara / Dodel, Richard / Pagenstecher, Axel / Neubauer, Andreas

European journal of cancer (Oxford, England : 1990)

2017

Language	English
Publishing date	2017-10-16
Publishing country	England
Document type	Letter
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2017.09.026
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Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 583: Show issues

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Article ; Online: l-DOPA-induced dyskinesia is associated with a deficient numerical downregulation of striatal tyrosine hydroxylase mRNA-expressing neurons.

Klietz, Martin / Keber, Ursula / Carlsson, Thomas / Chiu, Wei-Hua / Höglinger, Günter U / Weihe, Eberhard / Schäfer, Martin K-H / Depboylu, Candan

Neuroscience

2016 Volume 331, Page(s) 120–133

Abstract: l-3,4-Dihydroxyphenylalanine (l-DOPA) is the therapeutic gold standard in Parkinson's disease. However, most patients develop debilitating abnormal involuntary movements termed l-DOPA-induced dyskinesia (LID) as therapy-complicating side effects. The ... ...

Abstract	l-3,4-Dihydroxyphenylalanine (l-DOPA) is the therapeutic gold standard in Parkinson's disease. However, most patients develop debilitating abnormal involuntary movements termed l-DOPA-induced dyskinesia (LID) as therapy-complicating side effects. The underlying mechanisms of LID pathogenesis are still not fully understood. Recent evidence suggests an involvement of striatal tyrosine hydroxylase (TH) protein-expressing neurons, as they are capable of endogenously producing l-DOPA and possibly dopamine. The aim of this study was to elucidate changes of TH transcription in the striatum and nucleus accumbens that occur under experimental conditions of LID. Mice with a unilateral 6-hydroxydopamine-induced lesion of the medial forebrain bundle were treated daily with l-DOPA for 15days to provoke dyskinesia. In situ hybridization analysis revealed a significant numerical decrease of TH mRNA-positive neurons in the striatum and nucleus accumbens of mice not exhibiting LID, whereas dyskinetic animals failed to show this reduction of TH transcription. Interestingly, similar changes were observed in intact non-deafferentiated striata, demonstrating an l-DOPA-responsive transcriptional TH regulation independently from nigrostriatal lesion severity. Consolidation with our previous study on TH protein level (Keber et al., 2015) impressively highlights that LID is associated with both a deficient downregulation of TH transcription and an excessive translation of TH protein in intrastriatal neurons. As TH protein levels in comparison to mRNA levels showed a stronger correlation with development and severity of LID, antidyskinetic treatment strategies should focus on translational and posttranslational modulations of TH as a promising target.
MeSH term(s)	Animals ; Antiparkinson Agents/adverse effects ; Corpus Striatum/drug effects ; Corpus Striatum/metabolism ; Corpus Striatum/pathology ; Disease Models, Animal ; Down-Regulation/drug effects ; Dyskinesia, Drug-Induced/metabolism ; Dyskinesia, Drug-Induced/pathology ; Enkephalins/metabolism ; Levodopa/adverse effects ; Male ; Medial Forebrain Bundle ; Mice, Inbred C57BL ; Neuronal Plasticity ; Neurons/drug effects ; Neurons/metabolism ; Neurons/pathology ; Oxidopamine ; Protein Precursors/metabolism ; RNA, Messenger/metabolism ; Tyrosine 3-Monooxygenase/metabolism
Chemical Substances	Antiparkinson Agents ; Enkephalins ; Protein Precursors ; RNA, Messenger ; proenkephalin ; Levodopa (46627O600J) ; Oxidopamine (8HW4YBZ748) ; preproenkephalin (93443-35-7) ; Tyrosine 3-Monooxygenase (EC 1.14.16.2)
Language	English
Publishing date	2016-09-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2016.06.017
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Article ; Online: IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies: Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome.

Glöss, Stefanie / Jurmeister, Philipp / Thieme, Anne / Schmid, Simone / Cai, Wei Y / Serrette, Rene N / Perner, Sven / Ribbat-Idel, Julika / Pagenstecher, Axel / Bläker, Hendrik / Keber, Ursula / Stadelmann, Christine / Zechel, Sabrina / Johann, Pascal D / Hasselblatt, Martin / Paulus, Werner / Thomas, Christian / Dohmen, Hildegard / Baumhoer, Daniel /

Frank, Stephan / Agaimy, Abbas / Schüller, Ulrich / Vasudevaraja, Varshini / Snuderl, Matija / Liu, Cheng Z / Pfister, David G / Jungbluth, Achim A / Ghossein, Ronald A / Xu, Bin / Capper, David / Dogan, Snjezana

The American journal of surgical pathology

2021 Volume 45, Issue 9, Page(s) 1190–1204

Abstract: IDH2 R172 mutations occur in sinonasal undifferentiated carcinoma (SNUC), large-cell neuroendocrine carcinoma (LCNEC), sinonasal adenocarcinomas, and olfactory neuroblastoma (ONB). We performed a clinical, pathologic, and genetic/epigenetic analysis of a ...

Abstract	IDH2 R172 mutations occur in sinonasal undifferentiated carcinoma (SNUC), large-cell neuroendocrine carcinoma (LCNEC), sinonasal adenocarcinomas, and olfactory neuroblastoma (ONB). We performed a clinical, pathologic, and genetic/epigenetic analysis of a large IDH2-mutated sinonasal tumor cohort to explore their distinct features. A total 165 sinonasal/skull base tumors included 40 IDH2 mutants studied by light microscopy, immunohistochemistry, and genome-wide DNA methylation, and 125 IDH2 wild-type tumors used for comparison. Methylation profiles were analyzed by unsupervised hierarchical clustering, t-distributed stochastic neighbor embedding dimensionality reduction and assessed for copy number alterations (CNA). Thirty-nine histologically assessable cases included 25 (64.1%) SNUC, 8 (20.5%) LCNEC, 2 (5.1%) poorly differentiated adenocarcinomas, 1 (2.7%) ONB, and 3 (7.7%) IDH2-mutated tumors with ONB features. All cases were high-grade showing necrosis (82.4%), prominent nucleoli (88.9%), and median 21 mitoses/10 HPFs. AE1/AE3 and/or CAM 5.2 were positive in all and insulinoma-associated protein 1 (INSM1) in 80% cases. All IDH2 mutants formed one distinct group by t-distributed stochastic neighbor embedding dimensionality reduction separating from all IDH2 wild-type tumors. There was no correlation between methylation clusters and histopathologic diagnoses. Recurrent CNA included 1q gain (79.3%), 17p loss (75.9%), and 17q gain (58.6%). No CNA differences were observed between SNUC and LCNEC. IDH2 mutants showed better disease-specific survival than SMARCB1-deficient (P=0.027) and IDH2 wild-type carcinomas overall (P=0.042). IDH2-mutated sinonasal tumors are remarkably homogeneous at the molecular level and distinct from IDH2 wild-type sinonasal malignancies. Biology of IDH2-mutated sinonasal tumors might be primarily defined by their unique molecular fingerprint rather than by their respective histopathologic diagnoses.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Carcinoma/genetics ; Carcinoma/pathology ; Female ; Humans ; Isocitrate Dehydrogenase/genetics ; Male ; Middle Aged ; Mutation ; Neuroblastoma/genetics ; Neuroblastoma/pathology ; Paranasal Sinus Neoplasms/genetics ; Paranasal Sinus Neoplasms/pathology
Chemical Substances	IDH2 protein, human (EC 1.1.1.41) ; Isocitrate Dehydrogenase (EC 1.1.1.41)
Language	English
Publishing date	2021-07-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	752964-8
ISSN	1532-0979 ; 0147-5185
ISSN (online)	1532-0979
ISSN	0147-5185
DOI	10.1097/PAS.0000000000001697
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