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Papillary glioneuronal tumor (PGNT) exhibits a characteristic methylation profile and fusions involving PRKCA

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Harvard

Hou, Y, Pinheiro, J, Sahm, F, Reuss, DE, Schrimpf, D, Stichel, D, Casalini, B, Koelsche, C, Sievers, P, Wefers, AK, Reinhardt, A, Ebrahimi, A, Fernández-Klett, F, Pusch, S, Meier, J, Schweizer, L, Paulus, W, Prinz, M, Hartmann, C, Plate, KH, Reifenberger, G, Pietsch, T, Varlet, P, Pagès, M, Schüller, U, Scheie, D, de Stricker, K, Frank, S, Hench, J, Pollo, B, Brandner, S, Unterberg, A, Pfister, SM, Jones, DTW, Korshunov, A, Wick, W, Capper, D, Blümcke, I, von Deimling, A & Bertero, L 2019, 'Papillary glioneuronal tumor (PGNT) exhibits a characteristic methylation profile and fusions involving PRKCA' Acta Neuropathologica, vol. 137, no. 5, pp. 837-846. https://doi.org/10.1007/s00401-019-01969-2

APA

Hou, Y., Pinheiro, J., Sahm, F., Reuss, D. E., Schrimpf, D., Stichel, D., ... Bertero, L. (2019). Papillary glioneuronal tumor (PGNT) exhibits a characteristic methylation profile and fusions involving PRKCA. Acta Neuropathologica, 137(5), 837-846. https://doi.org/10.1007/s00401-019-01969-2

CBE

Hou Y, Pinheiro J, Sahm F, Reuss DE, Schrimpf D, Stichel D, Casalini B, Koelsche C, Sievers P, Wefers AK, Reinhardt A, Ebrahimi A, Fernández-Klett F, Pusch S, Meier J, Schweizer L, Paulus W, Prinz M, Hartmann C, Plate KH, Reifenberger G, Pietsch T, Varlet P, Pagès M, Schüller U, Scheie D, de Stricker K, Frank S, Hench J, Pollo B, Brandner S, Unterberg A, Pfister SM, Jones DTW, Korshunov A, Wick W, Capper D, Blümcke I, von Deimling A, Bertero L. 2019. Papillary glioneuronal tumor (PGNT) exhibits a characteristic methylation profile and fusions involving PRKCA. Acta Neuropathologica. 137(5):837-846. https://doi.org/10.1007/s00401-019-01969-2

MLA

Vancouver

Author

Hou, Yanghao ; Pinheiro, Jorge ; Sahm, Felix ; Reuss, David E ; Schrimpf, Daniel ; Stichel, Damian ; Casalini, Belén ; Koelsche, Christian ; Sievers, Philipp ; Wefers, Annika K ; Reinhardt, Annekathrin ; Ebrahimi, Azadeh ; Fernández-Klett, Francisco ; Pusch, Stefan ; Meier, Jochen ; Schweizer, Leonille ; Paulus, Werner ; Prinz, Marco ; Hartmann, Christian ; Plate, Karl H ; Reifenberger, Guido ; Pietsch, Torsten ; Varlet, Pascale ; Pagès, Mélanie ; Schüller, Ulrich ; Scheie, David ; de Stricker, Karin ; Frank, Stephan ; Hench, Jürgen ; Pollo, Bianca ; Brandner, Sebastian ; Unterberg, Andreas ; Pfister, Stefan M ; Jones, David T W ; Korshunov, Andrey ; Wick, Wolfgang ; Capper, David ; Blümcke, Ingmar ; von Deimling, Andreas ; Bertero, Luca. / Papillary glioneuronal tumor (PGNT) exhibits a characteristic methylation profile and fusions involving PRKCA. In: Acta Neuropathologica. 2019 ; Vol. 137, No. 5. pp. 837-846.

Bibtex

@article{1d229f295df9410cb7ea7e41495bd769,
title = "Papillary glioneuronal tumor (PGNT) exhibits a characteristic methylation profile and fusions involving PRKCA",
abstract = "Papillary glioneuronal tumor (PGNT) is a WHO-defined brain tumor entity that poses a major diagnostic challenge. Recently, SLC44A1-PRKCA fusions have been described in PGNT. We subjected 28 brain tumors from different institutions histologically diagnosed as PGNT to molecular and morphological analysis. Array-based methylation analysis revealed that 17/28 tumors exhibited methylation profiles typical for other tumor entities, mostly dysembryoplastic neuroepithelial tumor and hemispheric pilocytic astrocytoma. Conversely, 11/28 tumors exhibited a unique profile, thus constituting a distinct methylation class PGNT. By screening the extended Heidelberg cohort containing over 25,000 CNS tumors, we identified three additional tumors belonging to this methylation cluster but originally histologically diagnosed otherwise. RNA sequencing for the detection of SLC44A1-PRKCA fusions could be performed on 19 of the tumors, 10 of them belonging to the methylation class PGNT. In two additional cases, SLC44A1-PRKCA fusions were confirmed by FISH. We detected fusions involving PRKCA in all cases of this methylation class with material available for analyses: the canonical SLC44A1-PRKCA fusion was observed in 11/12 tumors, while the remaining case exhibited a NOTCH1-PRKCA fusion. Neither of the fusions was found in the tumors belonging to other methylation classes. Our results point towards a high misclassification rate of the morphological diagnosis PGNT and clearly demonstrate the necessity of molecular analyses. PRKCA fusions are highly diagnostic for PGNT, and detection by RNA sequencing enables the identification of rare fusion partners. Methylation analysis recognizes a unique methylation class PGNT irrespective of the nature of the PRKCA fusion.",
author = "Yanghao Hou and Jorge Pinheiro and Felix Sahm and Reuss, {David E} and Daniel Schrimpf and Damian Stichel and Bel{\'e}n Casalini and Christian Koelsche and Philipp Sievers and Wefers, {Annika K} and Annekathrin Reinhardt and Azadeh Ebrahimi and Francisco Fern{\'a}ndez-Klett and Stefan Pusch and Jochen Meier and Leonille Schweizer and Werner Paulus and Marco Prinz and Christian Hartmann and Plate, {Karl H} and Guido Reifenberger and Torsten Pietsch and Pascale Varlet and M{\'e}lanie Pag{\`e}s and Ulrich Sch{\"u}ller and David Scheie and {de Stricker}, Karin and Stephan Frank and J{\"u}rgen Hench and Bianca Pollo and Sebastian Brandner and Andreas Unterberg and Pfister, {Stefan M} and Jones, {David T W} and Andrey Korshunov and Wolfgang Wick and David Capper and Ingmar Bl{\"u}mcke and {von Deimling}, Andreas and Luca Bertero",
year = "2019",
month = "5",
doi = "10.1007/s00401-019-01969-2",
language = "English",
volume = "137",
pages = "837--846",
journal = "Acta Neuropathologica",
issn = "0001-6322",
publisher = "Springer",
number = "5",

}

RIS

TY - JOUR

T1 - Papillary glioneuronal tumor (PGNT) exhibits a characteristic methylation profile and fusions involving PRKCA

AU - Hou, Yanghao

AU - Pinheiro, Jorge

AU - Sahm, Felix

AU - Reuss, David E

AU - Schrimpf, Daniel

AU - Stichel, Damian

AU - Casalini, Belén

AU - Koelsche, Christian

AU - Sievers, Philipp

AU - Wefers, Annika K

AU - Reinhardt, Annekathrin

AU - Ebrahimi, Azadeh

AU - Fernández-Klett, Francisco

AU - Pusch, Stefan

AU - Meier, Jochen

AU - Schweizer, Leonille

AU - Paulus, Werner

AU - Prinz, Marco

AU - Hartmann, Christian

AU - Plate, Karl H

AU - Reifenberger, Guido

AU - Pietsch, Torsten

AU - Varlet, Pascale

AU - Pagès, Mélanie

AU - Schüller, Ulrich

AU - Scheie, David

AU - de Stricker, Karin

AU - Frank, Stephan

AU - Hench, Jürgen

AU - Pollo, Bianca

AU - Brandner, Sebastian

AU - Unterberg, Andreas

AU - Pfister, Stefan M

AU - Jones, David T W

AU - Korshunov, Andrey

AU - Wick, Wolfgang

AU - Capper, David

AU - Blümcke, Ingmar

AU - von Deimling, Andreas

AU - Bertero, Luca

PY - 2019/5

Y1 - 2019/5

N2 - Papillary glioneuronal tumor (PGNT) is a WHO-defined brain tumor entity that poses a major diagnostic challenge. Recently, SLC44A1-PRKCA fusions have been described in PGNT. We subjected 28 brain tumors from different institutions histologically diagnosed as PGNT to molecular and morphological analysis. Array-based methylation analysis revealed that 17/28 tumors exhibited methylation profiles typical for other tumor entities, mostly dysembryoplastic neuroepithelial tumor and hemispheric pilocytic astrocytoma. Conversely, 11/28 tumors exhibited a unique profile, thus constituting a distinct methylation class PGNT. By screening the extended Heidelberg cohort containing over 25,000 CNS tumors, we identified three additional tumors belonging to this methylation cluster but originally histologically diagnosed otherwise. RNA sequencing for the detection of SLC44A1-PRKCA fusions could be performed on 19 of the tumors, 10 of them belonging to the methylation class PGNT. In two additional cases, SLC44A1-PRKCA fusions were confirmed by FISH. We detected fusions involving PRKCA in all cases of this methylation class with material available for analyses: the canonical SLC44A1-PRKCA fusion was observed in 11/12 tumors, while the remaining case exhibited a NOTCH1-PRKCA fusion. Neither of the fusions was found in the tumors belonging to other methylation classes. Our results point towards a high misclassification rate of the morphological diagnosis PGNT and clearly demonstrate the necessity of molecular analyses. PRKCA fusions are highly diagnostic for PGNT, and detection by RNA sequencing enables the identification of rare fusion partners. Methylation analysis recognizes a unique methylation class PGNT irrespective of the nature of the PRKCA fusion.

AB - Papillary glioneuronal tumor (PGNT) is a WHO-defined brain tumor entity that poses a major diagnostic challenge. Recently, SLC44A1-PRKCA fusions have been described in PGNT. We subjected 28 brain tumors from different institutions histologically diagnosed as PGNT to molecular and morphological analysis. Array-based methylation analysis revealed that 17/28 tumors exhibited methylation profiles typical for other tumor entities, mostly dysembryoplastic neuroepithelial tumor and hemispheric pilocytic astrocytoma. Conversely, 11/28 tumors exhibited a unique profile, thus constituting a distinct methylation class PGNT. By screening the extended Heidelberg cohort containing over 25,000 CNS tumors, we identified three additional tumors belonging to this methylation cluster but originally histologically diagnosed otherwise. RNA sequencing for the detection of SLC44A1-PRKCA fusions could be performed on 19 of the tumors, 10 of them belonging to the methylation class PGNT. In two additional cases, SLC44A1-PRKCA fusions were confirmed by FISH. We detected fusions involving PRKCA in all cases of this methylation class with material available for analyses: the canonical SLC44A1-PRKCA fusion was observed in 11/12 tumors, while the remaining case exhibited a NOTCH1-PRKCA fusion. Neither of the fusions was found in the tumors belonging to other methylation classes. Our results point towards a high misclassification rate of the morphological diagnosis PGNT and clearly demonstrate the necessity of molecular analyses. PRKCA fusions are highly diagnostic for PGNT, and detection by RNA sequencing enables the identification of rare fusion partners. Methylation analysis recognizes a unique methylation class PGNT irrespective of the nature of the PRKCA fusion.

U2 - 10.1007/s00401-019-01969-2

DO - 10.1007/s00401-019-01969-2

M3 - Journal article

VL - 137

SP - 837

EP - 846

JO - Acta Neuropathologica

JF - Acta Neuropathologica

SN - 0001-6322

IS - 5

ER -

ID: 59040096