PortalPublikationenIDH2 R172 Mutations Across Poorly Differentiated Sinonasal T...

IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies

Standard

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.

in: AM J SURG PATHOL, Jahrgang 45, Nr. 9, 01.09.2021, S. 1190-1204.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Glöss, S, Jurmeister, P, Thieme, A, Schmid, S, Cai, WY, Serrette, RN, Perner, S, Ribbat-Idel, J, Pagenstecher, A, Bläker, H, Keber, U, Stadelmann, C, Zechel, S, Johann, PD, Hasselblatt, M, Paulus, W, Thomas, C, Dohmen, H, Baumhoer, D, Frank, S, Agaimy, A, Schüller, U, Vasudevaraja, V, Snuderl, M, Liu, CZ, Pfister, DG, Jungbluth, AA, Ghossein, RA, Xu, B, Capper, D & Dogan, S 2021, 'IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies: Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome', AM J SURG PATHOL, Jg. 45, Nr. 9, S. 1190-1204. https://doi.org/10.1097/PAS.0000000000001697

APA

Glöss, S., Jurmeister, P., Thieme, A., 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., Hasselblatt, M., Paulus, W., Thomas, C., Dohmen, H., Baumhoer, D., ... Dogan, S. (2021). IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies: Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome. AM J SURG PATHOL, 45(9), 1190-1204. https://doi.org/10.1097/PAS.0000000000001697

Vancouver

Glöss S, Jurmeister P, Thieme A, Schmid S, Cai WY, Serrette RN et al. IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies: Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome. AM J SURG PATHOL. 2021 Sep 1;45(9):1190-1204. https://doi.org/10.1097/PAS.0000000000001697

Bibtex

@article{4f1382acd42c48c781b2f4b5f7118c37,
title = "IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies: Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome",
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.",
keywords = "Adult, Aged, Aged, 80 and over, Carcinoma/genetics, Female, Humans, Isocitrate Dehydrogenase/genetics, Male, Middle Aged, Mutation, Neuroblastoma/genetics, Paranasal Sinus Neoplasms/genetics",
author = "Stefanie Gl{\"o}ss and Philipp Jurmeister and Anne Thieme and Simone Schmid and Cai, {Wei Y} and Serrette, {Rene N} and Sven Perner and Julika Ribbat-Idel and Axel Pagenstecher and Hendrik Bl{\"a}ker and Ursula Keber and Christine Stadelmann and Sabrina Zechel and Johann, {Pascal D} and Martin Hasselblatt and Werner Paulus and Christian Thomas and Hildegard Dohmen and Daniel Baumhoer and Stephan Frank and Abbas Agaimy and Ulrich Sch{\"u}ller and Varshini Vasudevaraja and Matija Snuderl and Liu, {Cheng Z} and Pfister, {David G} and Jungbluth, {Achim A} and Ghossein, {Ronald A} and Bin Xu and David Capper and Snjezana Dogan",
note = "Copyright {\textcopyright} 2021 Wolters Kluwer Health, Inc. All rights reserved.",
year = "2021",
month = sep,
day = "1",
doi = "10.1097/PAS.0000000000001697",
language = "English",
volume = "45",
pages = "1190--1204",
journal = "AM J SURG PATHOL",
issn = "0147-5185",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

RIS

TY - JOUR

T1 - IDH2 R172 Mutations Across Poorly Differentiated Sinonasal Tract Malignancies

T2 - Forty Molecularly Homogenous and Histologically Variable Cases With Favorable Outcome

AU - Glöss, Stefanie

AU - Jurmeister, Philipp

AU - Thieme, Anne

AU - Schmid, Simone

AU - Cai, Wei Y

AU - Serrette, Rene N

AU - Perner, Sven

AU - Ribbat-Idel, Julika

AU - Pagenstecher, Axel

AU - Bläker, Hendrik

AU - Keber, Ursula

AU - Stadelmann, Christine

AU - Zechel, Sabrina

AU - Johann, Pascal D

AU - Hasselblatt, Martin

AU - Paulus, Werner

AU - Thomas, Christian

AU - Dohmen, Hildegard

AU - Baumhoer, Daniel

AU - Frank, Stephan

AU - Agaimy, Abbas

AU - Schüller, Ulrich

AU - Vasudevaraja, Varshini

AU - Snuderl, Matija

AU - Liu, Cheng Z

AU - Pfister, David G

AU - Jungbluth, Achim A

AU - Ghossein, Ronald A

AU - Xu, Bin

AU - Capper, David

AU - Dogan, Snjezana

N1 - Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2021/9/1

Y1 - 2021/9/1

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Carcinoma/genetics

KW - Female

KW - Humans

KW - Isocitrate Dehydrogenase/genetics

KW - Male

KW - Middle Aged

KW - Mutation

KW - Neuroblastoma/genetics

KW - Paranasal Sinus Neoplasms/genetics

U2 - 10.1097/PAS.0000000000001697

DO - 10.1097/PAS.0000000000001697

M3 - SCORING: Journal article

C2 - 34265800

VL - 45

SP - 1190

EP - 1204

JO - AM J SURG PATHOL

JF - AM J SURG PATHOL

SN - 0147-5185

IS - 9

ER -