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Histologically distinct neuroepithelial tumors with histone 3 G34 mutation are molecularly similar and comprise a single nosologic entity

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Histologically distinct neuroepithelial tumors with histone 3 G34 mutation are molecularly similar and comprise a single nosologic entity. / Korshunov, Andrey; Capper, David; Reuss, David; Schrimpf, Daniel; Ryzhova, Marina; Hovestadt, Volker; Sturm, Dominik; Meyer, Jochen; Jones, Chris; Zheludkova, Olga; Kumirova, Ella; Golanov, Andrey; Kool, Marcel; Schüller, Ulrich; Mittelbronn, Michel; Hasselblatt, Martin; Schittenhelm, Jens; Reifenberger, Guido; Herold-Mende, Christel; Lichter, Peter; Deimling, Andreas; Pfister, Stefan M; Jones, David T W.

in: ACTA NEUROPATHOL, Jahrgang 131, Nr. 1, 01.2016, S. 137-46.

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

Harvard

Korshunov, A, Capper, D, Reuss, D, Schrimpf, D, Ryzhova, M, Hovestadt, V, Sturm, D, Meyer, J, Jones, C, Zheludkova, O, Kumirova, E, Golanov, A, Kool, M, Schüller, U, Mittelbronn, M, Hasselblatt, M, Schittenhelm, J, Reifenberger, G, Herold-Mende, C, Lichter, P, Deimling, A, Pfister, SM & Jones, DTW 2016, 'Histologically distinct neuroepithelial tumors with histone 3 G34 mutation are molecularly similar and comprise a single nosologic entity', ACTA NEUROPATHOL, Jg. 131, Nr. 1, S. 137-46. https://doi.org/10.1007/s00401-015-1493-1

APA

Korshunov, A., Capper, D., Reuss, D., Schrimpf, D., Ryzhova, M., Hovestadt, V., Sturm, D., Meyer, J., Jones, C., Zheludkova, O., Kumirova, E., Golanov, A., Kool, M., Schüller, U., Mittelbronn, M., Hasselblatt, M., Schittenhelm, J., Reifenberger, G., Herold-Mende, C., ... Jones, D. T. W. (2016). Histologically distinct neuroepithelial tumors with histone 3 G34 mutation are molecularly similar and comprise a single nosologic entity. ACTA NEUROPATHOL, 131(1), 137-46. https://doi.org/10.1007/s00401-015-1493-1

Vancouver

Korshunov A, Capper D, Reuss D, Schrimpf D, Ryzhova M, Hovestadt V et al. Histologically distinct neuroepithelial tumors with histone 3 G34 mutation are molecularly similar and comprise a single nosologic entity. ACTA NEUROPATHOL. 2016 Jan;131(1):137-46. https://doi.org/10.1007/s00401-015-1493-1

Bibtex

@article{82844ab7f6d242f2b5112e6cac5124ff,
title = "Histologically distinct neuroepithelial tumors with histone 3 G34 mutation are molecularly similar and comprise a single nosologic entity",
abstract = "In contrast to the relative morphological uniformity of histone H3 K27-mutant high-grade gliomas, H3 G34-mutant tumors present as a histopathologically heterogeneous group of neoplasms, with microscopic characteristics typical of either glioblastoma (GBM) or central nervous system primitive neuroectodermal tumors (CNS-PNET). In the current study, we performed an integrative clinical, histopathological and molecular analysis of 81 G34-mutant CNS tumors. Routinely prepared tumor tissues were investigated for genomic and epigenomic alterations. Despite their divergent histopathological appearance, CNS tumors with H3.3 G34 mutations displayed uniform epigenetic signatures, suggesting a single biological origin. Comparative cytogenetic analysis with other GBM subtypes disclosed a high frequency and high specificity of 3q and 4q loss across G34-mutant tumors. PDGFRA amplification was more common in cases with GBM than with PNET morphology (36 vs. 5 %, respectively), while CCND2 amplifications showed the opposite trend (5 vs. 27 %). Survival analysis revealed the presence of amplified oncogene(s) and MGMT methylation as independent prognostic markers for poor and favorable outcomes, respectively. No difference in outcome was found between morphological variants (GBM vs. PNET). Thus, different histological variants of G34-mutant CNS tumors likely comprise a single biological entity (high-grade glioma with H3 G34 mutation, HGG_G34), which should be outlined in future diagnostic and therapeutic classifications. Screening for H3.3 G34 mutation should therefore be recommended as a routine diagnostic marker for supratentorial CNS tumors across a broad histological spectrum.",
keywords = "Adolescent, Adult, Central Nervous System Neoplasms, Child, Epigenomics, Female, Glioblastoma, Glioma, Histones, Humans, Male, Middle Aged, Mutation, Supratentorial Neoplasms, Young Adult, Journal Article",
author = "Andrey Korshunov and David Capper and David Reuss and Daniel Schrimpf and Marina Ryzhova and Volker Hovestadt and Dominik Sturm and Jochen Meyer and Chris Jones and Olga Zheludkova and Ella Kumirova and Andrey Golanov and Marcel Kool and Ulrich Sch{\"u}ller and Michel Mittelbronn and Martin Hasselblatt and Jens Schittenhelm and Guido Reifenberger and Christel Herold-Mende and Peter Lichter and Andreas Deimling and Pfister, {Stefan M} and Jones, {David T W}",
year = "2016",
month = jan,
doi = "10.1007/s00401-015-1493-1",
language = "English",
volume = "131",
pages = "137--46",
journal = "ACTA NEUROPATHOL",
issn = "0001-6322",
publisher = "Springer",
number = "1",

}

RIS

TY - JOUR

T1 - Histologically distinct neuroepithelial tumors with histone 3 G34 mutation are molecularly similar and comprise a single nosologic entity

AU - Korshunov, Andrey

AU - Capper, David

AU - Reuss, David

AU - Schrimpf, Daniel

AU - Ryzhova, Marina

AU - Hovestadt, Volker

AU - Sturm, Dominik

AU - Meyer, Jochen

AU - Jones, Chris

AU - Zheludkova, Olga

AU - Kumirova, Ella

AU - Golanov, Andrey

AU - Kool, Marcel

AU - Schüller, Ulrich

AU - Mittelbronn, Michel

AU - Hasselblatt, Martin

AU - Schittenhelm, Jens

AU - Reifenberger, Guido

AU - Herold-Mende, Christel

AU - Lichter, Peter

AU - Deimling, Andreas

AU - Pfister, Stefan M

AU - Jones, David T W

PY - 2016/1

Y1 - 2016/1

N2 - In contrast to the relative morphological uniformity of histone H3 K27-mutant high-grade gliomas, H3 G34-mutant tumors present as a histopathologically heterogeneous group of neoplasms, with microscopic characteristics typical of either glioblastoma (GBM) or central nervous system primitive neuroectodermal tumors (CNS-PNET). In the current study, we performed an integrative clinical, histopathological and molecular analysis of 81 G34-mutant CNS tumors. Routinely prepared tumor tissues were investigated for genomic and epigenomic alterations. Despite their divergent histopathological appearance, CNS tumors with H3.3 G34 mutations displayed uniform epigenetic signatures, suggesting a single biological origin. Comparative cytogenetic analysis with other GBM subtypes disclosed a high frequency and high specificity of 3q and 4q loss across G34-mutant tumors. PDGFRA amplification was more common in cases with GBM than with PNET morphology (36 vs. 5 %, respectively), while CCND2 amplifications showed the opposite trend (5 vs. 27 %). Survival analysis revealed the presence of amplified oncogene(s) and MGMT methylation as independent prognostic markers for poor and favorable outcomes, respectively. No difference in outcome was found between morphological variants (GBM vs. PNET). Thus, different histological variants of G34-mutant CNS tumors likely comprise a single biological entity (high-grade glioma with H3 G34 mutation, HGG_G34), which should be outlined in future diagnostic and therapeutic classifications. Screening for H3.3 G34 mutation should therefore be recommended as a routine diagnostic marker for supratentorial CNS tumors across a broad histological spectrum.

AB - In contrast to the relative morphological uniformity of histone H3 K27-mutant high-grade gliomas, H3 G34-mutant tumors present as a histopathologically heterogeneous group of neoplasms, with microscopic characteristics typical of either glioblastoma (GBM) or central nervous system primitive neuroectodermal tumors (CNS-PNET). In the current study, we performed an integrative clinical, histopathological and molecular analysis of 81 G34-mutant CNS tumors. Routinely prepared tumor tissues were investigated for genomic and epigenomic alterations. Despite their divergent histopathological appearance, CNS tumors with H3.3 G34 mutations displayed uniform epigenetic signatures, suggesting a single biological origin. Comparative cytogenetic analysis with other GBM subtypes disclosed a high frequency and high specificity of 3q and 4q loss across G34-mutant tumors. PDGFRA amplification was more common in cases with GBM than with PNET morphology (36 vs. 5 %, respectively), while CCND2 amplifications showed the opposite trend (5 vs. 27 %). Survival analysis revealed the presence of amplified oncogene(s) and MGMT methylation as independent prognostic markers for poor and favorable outcomes, respectively. No difference in outcome was found between morphological variants (GBM vs. PNET). Thus, different histological variants of G34-mutant CNS tumors likely comprise a single biological entity (high-grade glioma with H3 G34 mutation, HGG_G34), which should be outlined in future diagnostic and therapeutic classifications. Screening for H3.3 G34 mutation should therefore be recommended as a routine diagnostic marker for supratentorial CNS tumors across a broad histological spectrum.

KW - Adolescent

KW - Adult

KW - Central Nervous System Neoplasms

KW - Child

KW - Epigenomics

KW - Female

KW - Glioblastoma

KW - Glioma

KW - Histones

KW - Humans

KW - Male

KW - Middle Aged

KW - Mutation

KW - Supratentorial Neoplasms

KW - Young Adult

KW - Journal Article

U2 - 10.1007/s00401-015-1493-1

DO - 10.1007/s00401-015-1493-1

M3 - SCORING: Journal article

C2 - 26482474

VL - 131

SP - 137

EP - 146

JO - ACTA NEUROPATHOL

JF - ACTA NEUROPATHOL

SN - 0001-6322

IS - 1

ER -