Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "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)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

• MeSH
• Child MeSH
• Forkhead Transcription Factors genetics   MeSH
• Humans MeSH
• DNA Methylation * MeSH
• Molecular Sequence Data MeSH
• Tumor Suppressor Proteins genetics   MeSH
• Central Nervous System Neoplasms classification   diagnosis   genetics   pathology   MeSH
• Neuroectodermal Tumors classification   diagnosis   genetics   pathology   MeSH
• Proto-Oncogene Proteins chemistry   genetics   MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Repressor Proteins chemistry   genetics   MeSH
• Amino Acid Sequence MeSH
• Signal Transduction MeSH
• Gene Expression Profiling MeSH
• Trans-Activators MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• BCOR protein, human MeSH Browser
• CIC protein, human MeSH Browser
• Forkhead Transcription Factors MeSH
• FOXR2 protein, human MeSH Browser
• MN1 protein, human MeSH Browser
• Tumor Suppressor Proteins MeSH
• Proto-Oncogene Proteins MeSH
• Repressor Proteins MeSH
• Trans-Activators MeSH