title: New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.
abstract: 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.
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authors.affiliation: Division of Molecular Genetics, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.|Heidelberg Center for Personalized Oncology, DKFZ-HIPO, DKFZ, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
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authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.|Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
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authors.lastname: Ellison
authors.affiliation: Department of Neuropathology, Heidelberg University Hospital, 69120 Heidelberg, Germany.|Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), 69120 Heidelberg.
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mesh_terms: D000595:Amino Acid Sequence; D016543:Central Nervous System Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D002648:Child; D019175:DNA Methylation; D051858:Forkhead Transcription Factors / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D017599:Neuroectodermal Tumors / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C411984:BCOR protein, human; C498610:CIC protein, human; C499816:FOXR2 protein, human; D051858:Forkhead Transcription Factors; C506524:MN1 protein, human; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins