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

Journal article

Publication Details

Author(s): 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 DT, Korshunov A, Wick W, Capper D, Blümcke I, von Deimling A, Bertero L
Journal: Acta Neuropathologica
Publication year: 2019
Volume: 137
Journal issue: 5
Pages range: 837-846
ISSN: 0001-6322
eISSN: 1432-0533


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.

FAU Authors / FAU Editors

Blümcke, Ingmar Prof. Dr.
Lehrstuhl für Neuropathologie

External institutions with authors

Albert-Ludwigs-Universität Freiburg
Deutsches Krebsforschungszentrum (DKFZ)
Foundation of the Carlo Besta Neurological Institute (IRCCS)
Hopp-Kindertumorzentrum Heidelberg - KiTZ
Hospital de São João / Saint John Hospital
Humboldt-Universität zu Berlin
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Rheinische Friedrich-Wilhelms-Universität Bonn
UCL Institute of Neurology
Universitätsklinikum Düsseldorf
Universitätsklinikum Frankfurt
Universitätsklinikum Hamburg-Eppendorf
Universitätsklinikum Heidelberg
Universitätsklinikum Münster
Universitätsspital Basel
University of Paris 5 - René Descartes / Université Paris V René Descartes

How to cite

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.

Hou, Yanghao, et al. "Papillary glioneuronal tumor (PGNT) exhibits a characteristic methylation profile and fusions involving PRKCA." Acta Neuropathologica 137.5 (2019): 837-846.


Last updated on 2019-28-05 at 15:48