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
• 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

We report four cases of uterine tumors with neuroectodermal differentiation. One tumor had neuroectodermal component only; in the three other tumors, the neuroectodermal component was admixed with another component, namely rhabdomyosarcoma (1 case), and endometrioid adenocarcinoma (2 cases). Histologically, the neuroectodermal component consisted of small to medium sized cells arranged in diffuse sheets. The tumor cells had round nuclei with stippled to coarsely granular chromatin, mostly with non-prominent nucleoli, and scant eosinophilic or amphophilic cytoplasm. Immunohistochemically, 4/4 tumors showed expression of vimentin, synaptophysin and CD56; 3/4 tumors were CD99 and NSE positive; 2/4 tumors showed focal expression of S-100 protein; and 1/4 tumors had focal dot-like cytoplasmic positivity for cytokeratin AE1/AE3. FLI-1 was negative in all cases. FISH examination was performed and none of the tumors showed rearrangement of EWSR1 gene. Uterine tumors with neuroectodermal differentiation are rare; to the best of our knowledge only 44 cases have been reported in the literature to date, referred to as Ewing sarcoma, peripheral PNET (pPNET), PNET (not otherwise specified) and uterine tumors with neuroendocrine differentiation.

• MeSH
• Cell Differentiation physiology   MeSH
• Gene Rearrangement MeSH
• Immunohistochemistry MeSH
• Middle Aged MeSH
• Humans MeSH
• Uterine Neoplasms genetics   pathology   MeSH
• Neuroectodermal Tumors genetics   pathology   MeSH
• Calmodulin-Binding Proteins genetics   MeSH
• RNA-Binding Proteins genetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH

• Keywords
• geny Bmi1 a Ezh2, proteiny rodiny PcG,
• MeSH
• Gene Expression * genetics   immunology   drug effects   MeSH
• Immunohistochemistry methods   trends   utilization   MeSH
• Clinical Laboratory Techniques methods   utilization   MeSH
• Medical Oncology methods   trends   MeSH
• Humans MeSH
• Cell Line, Tumor microbiology   drug effects   MeSH
• Neuroectodermal Tumors * diagnosis   etiology   genetics   MeSH
• Polycomb-Group Proteins genetics   isolation & purification   MeSH
• Statistics as Topic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Research Support as Topic MeSH
• Immunohistochemistry MeSH
• Humans MeSH
• Medulloblastoma genetics   MeSH
• Tumor Suppressor Protein p53 MeSH
• Neuroectodermal Tumors genetics   MeSH
• Pilot Projects MeSH
• Polymerase Chain Reaction MeSH
• Prognosis MeSH
• Gene Expression Regulation, Neoplastic genetics   immunology   MeSH
• Base Sequence MeSH
• Check Tag
• Humans MeSH

Projekt se týká vztahu buněčné diferenciace a maligní transformace u malobuněčného karcinomu genů a faktorů specifických pro buněčnou diferenciaci a jejich transkripční regulace. XXX XXX XXX

• MeSH
• Carcinoma, Small Cell genetics   diagnosis   MeSH
• Biomarkers, Tumor MeSH
• Neuroectodermal Tumors genetics   diagnosis   MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• onkologie
• pneumologie a ftizeologie
• embryologie a teratologie
• genetika, lékařská genetika
• NML Publication type
• závěrečné zprávy o řešení grantu IGA MZ ČR