Papillary glioneuronal tumor (PGNT) exhibits a characteristic methylation profile and fusions involving PRKCA
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Papillary glioneuronal tumor (PGNT) exhibits a characteristic methylation profile and fusions involving PRKCA. / 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.
In: ACTA NEUROPATHOL, Vol. 137, No. 5, 05.2019, p. 837-846.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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.
KW - Journal Article
U2 - 10.1007/s00401-019-01969-2
DO - 10.1007/s00401-019-01969-2
M3 - SCORING: Journal article
C2 - 30759284
VL - 137
SP - 837
EP - 846
JO - ACTA NEUROPATHOL
JF - ACTA NEUROPATHOL
SN - 0001-6322
IS - 5
ER -
