Molecular identification of CNS NB-FOXR2, CNS EFT-CIC, CNS HGNET-MN1 and CNS HGNET-BCOR pediatric brain tumors using tumor-specific signature genes

• Published in: Acta neuropathologica communications Vol. 8; no. 1; pp. 1 - 105
• Main Authors: Åastowska, Maria, Trubicka, Joanna, SobociÅska, Anna, Wojtas, Bartosz, Niemira, Magdalena, SzaÅkowska, Anna, KrÄtowski, Adam, KarkuciÅska-WiÄckowska, Agnieszka, Kaleta, Magdalena, Ejmont, Maria, Perek-Polnik, Marta, Dembowska-BagiÅska, Bożenna, Grajkowska, WiesÅawa, Matyja, Ewa
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 10.07.2020; BioMed Central; BMC
• Subjects: Brain cancer; Brain tumors; Classification; CNS EFT-CIC; CNS HGNET-BCOR; CNS HGNET-MN1; CNS NB-FOXR2; Deoxyribonucleic acid; DNA; DNA methylation; Ewings sarcoma; Formaldehyde; Gene expression; Genes; Genes expression; Genetic aspects; Genomes; Identification; Medical research; Methylation; Nervous system; Pediatrics; Sarcoma; Software; Transcription (Genetics); Tumors; Poland; United States > US
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-020-00984-9

Four molecular types of rare central nervous system (CNS) tumors have been recently identified by gene methylation profiling: CNS Neuroblastoma with FOXR2 activation (CNS NB-FOXR2), CNS Ewing Sarcoma Family Tumor with CIC alteration (CNS EFT-CIC), CNS high grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1) and CNS high grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR). Although they are not represented in 2016 updated WHO classification of CNS tumors, their diagnostic recognition is important because of clinical consequences. We have introduced a diagnostic method based on transcription profiling of tumor specific signature genes from formalin-fixed, paraffin-embedded tumor blocks using NanoString nCounter Technology. Altogether, 14 out of 187 (7.4%) high grade pediatric brain tumors were diagnosed with either of four new CNS categories. Histopathological examination of the tumors confirmed, that they demonstrate a spectrum of morphology mimicking other CNS high grade tumors. However, they also exhibit some suggestive histopathological and immunohistochemical features that allow for a presumptive diagnosis prior to molecular assessment. Clinical characteristics of patients corroborated with the previous findings for CNS EFT-CIC, CNS NB-FOXR2 and CNS HGNET-MN1 patients, with a favorable survival rate for the latter two groups. Among six CNS HGNET-BCOR patients, three patients are long term survivors, suggesting possible heterogeneity within this molecular category of tumors. In summary, we confirmed the effectiveness of NanoString method using a single, multi-gene tumor specific signature and recommend this novel approach for identification of either one of the four newly described CNS tumor entities. Keywords: Brain tumors, CNS EFT-CIC, CNS NB-FOXR2, CNS HGNET-MN1, CNS HGNET-BCOR, Genes expression