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000169840 1001_ $$0P:(DE-He78)766063bc14996d73b7b17b5017c8fcba$$aGlöss, Stefanie$$b0$$udkfz
000169840 245__ $$aIDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies: Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome.
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000169840 500__ $$a2021 Sep 1;45(9):1190-1204
000169840 520__ $$aIDH2 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.
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000169840 7001_ $$aJurmeister, Philipp$$b1
000169840 7001_ $$0P:(DE-He78)21f693ba604e9286be3b25068b440d08$$aThieme, Anne$$b2$$udkfz
000169840 7001_ $$aSchmid, Simone$$b3
000169840 7001_ $$aCai, Wei Y$$b4
000169840 7001_ $$aSerrette, Rene N$$b5
000169840 7001_ $$aPerner, Sven$$b6
000169840 7001_ $$aRibbat-Idel, Julika$$b7
000169840 7001_ $$aPagenstecher, Axel$$b8
000169840 7001_ $$aBläker, Hendrik$$b9
000169840 7001_ $$aKeber, Ursula$$b10
000169840 7001_ $$aStadelmann, Christine$$b11
000169840 7001_ $$aZechel, Sabrina$$b12
000169840 7001_ $$0P:(DE-He78)3fdc3623477264cb5d0e14f256dbfbb8$$aJohann, Pascal D$$b13$$udkfz
000169840 7001_ $$aHasselblatt, Martin$$b14
000169840 7001_ $$aPaulus, Werner$$b15
000169840 7001_ $$aThomas, Christian$$b16
000169840 7001_ $$aDohmen, Hildegard$$b17
000169840 7001_ $$aBaumhoer, Daniel$$b18
000169840 7001_ $$aFrank, Stephan$$b19
000169840 7001_ $$aAgaimy, Abbas$$b20
000169840 7001_ $$aSchüller, Ulrich$$b21
000169840 7001_ $$aVasudevaraja, Varshini$$b22
000169840 7001_ $$aSnuderl, Matija$$b23
000169840 7001_ $$aLiu, Cheng Z$$b24
000169840 7001_ $$aPfister, David G$$b25
000169840 7001_ $$aJungbluth, Achim A$$b26
000169840 7001_ $$aGhossein, Ronald A$$b27
000169840 7001_ $$aXu, Bin$$b28
000169840 7001_ $$0P:(DE-He78)51bf9ae9cb5771b30c483e5597ef606c$$aCapper, David$$b29$$udkfz
000169840 7001_ $$aDogan, Snjezana$$b30
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