Molecular analysis of pediatric CNS-PNET revealed nosologic heterogeneity and potent diagnostic markers for CNS neuroblastoma with FOXR2-activation

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly malignant neoplasms posing diagnostic challenge due to a lack of defining molecular markers. CNS neuroblastoma with forkhead box R2 (FOXR2) activation (CNS_NBL) emerged as a distinct pediatric brain tumor entity fr...

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Bibliographic Details
Published in:Acta neuropathologica communications 2021-02, Vol.9 (1), p.20-20, Article 20
Main Authors: Korshunov, Andrey, Okonechnikov, Konstantin, Schmitt-Hoffner, Felix, Ryzhova, Marina, Sahm, Felix, Stichel, Damian, Schrimpf, Daniel, Reuss, David E, Sievers, Philipp, Suwala, Abigail Kora, Kumirova, Ella, Zheludkova, Olga, Golanov, Andrey, Jones, David T W, Pfister, Stefan M, Kool, Marcel, von Deimling, Andreas
Format: Article
Language:English
Subjects:
Analysis
Automation
Brain cancer
Brain tumors
Classification
CNS-PNET
Deoxyribonucleic acid
DNA
DNA methylation
Epigenetic inheritance
Ewings sarcoma
FOXR2-activation
Gene expression
Genes
Gliomas
Methylation
Nervous system
Neuroblastoma
Patients
Pediatrics
Performance evaluation
Principal components analysis
RNA
SOX10
Tumors
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Summary:Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly malignant neoplasms posing diagnostic challenge due to a lack of defining molecular markers. CNS neuroblastoma with forkhead box R2 (FOXR2) activation (CNS_NBL) emerged as a distinct pediatric brain tumor entity from a pool previously diagnosed as primitive neuroectodermal tumors of the central nervous system (CNS-PNETs). Current standard of identifying CNS_NBL relies on molecular analysis. We set out to establish immunohistochemical markers allowing safely distinguishing CNS_NBL from morphological mimics. To this aim we analyzed a series of 84 brain tumors institutionally diagnosed as CNS-PNET. As expected, epigenetic analysis revealed different methylation groups corresponding to the (1) CNS-NBL (24%), (2) glioblastoma IDH wild-type subclass H3.3 G34 (26%), (3) glioblastoma IDH wild-type subclass MYCN (21%) and (4) ependymoma with RELA_C11orf95 fusion (29%) entities. Transcriptome analysis of this series revealed a set of differentially expressed genes distinguishing CNS_NBL from its mimics. Based on RNA-sequencing data we established SOX10 and ANKRD55 expression as genes discriminating CNS_NBL from other tumors exhibiting CNS-PNET. Immunohistochemical detection of combined expression of SOX10 and ANKRD55 clearly identifies CNS_NBL discriminating them to other hemispheric CNS neoplasms harboring "PNET-like" microscopic appearance. Owing the rarity of CNS_NBL, a confirmation of the elaborated diagnostic IHC algorithm will be necessary in prospective patient series.
ISSN:2051-5960
2051-5960
DOI:10.1186/s40478-021-01118-5