Journal Article

DKFZ-2021-01583

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies: Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome.

Glöss, S.DKFZ* ; Jurmeister, P. ; Thieme, A.DKFZ* ; Schmid, S. ; Cai, W. Y. ; Serrette, R. N. ; Perner, S. ; Ribbat-Idel, J. ; Pagenstecher, A. ; Bläker, H. ; Keber, U. ; Stadelmann, C. ; Zechel, S. ; Johann, P. D.DKFZ* ; Hasselblatt, M. ; Paulus, W. ; Thomas, C. ; Dohmen, H. ; Baumhoer, D. ; Frank, S. ; Agaimy, A. ; Schüller, U. ; Vasudevaraja, V. ; Snuderl, M. ; Liu, C. Z. ; Pfister, D. G. ; Jungbluth, A. A. ; Ghossein, R. A. ; Xu, B. ; Capper, D.DKFZ* ; Dogan, S.

2021
Ovid [S.l.]

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Please use a persistent id in citations: doi:10.1097/PAS.0000000000001697

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.

Note: 2021 Sep 1;45(9):1190-1204

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Contributing Institute(s):

1. DKTK BE zentral (BE01)
2. B062 Pädiatrische Neuroonkologie (B062)
3. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2021

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Database coverage:
; Allianz-Lizenz ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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