SWI/SNF deficient central nervous system neoplasms |
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| Institution: | 1. Pathology Department, Instituto Valenciano de Oncología, Valencia, Spain;2. Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan;3. Molecular Biology Laboratory, Pathology Department, University of Valencia, Spain;4. Departamento de Patología & Diagnóstico Molecular, Hospital de Cáncer de Barretos, Barretos, Sao Paulo, Brazil;5. Pathology Department, University of Valencia, Valencia, Spain;6. Medical Oncology, Instituto Valenciano de Oncología, Valencia, Spain;7. Department of Pathology, ASST - Centro Specialistico Ortopedico Traumatologico Gaetano PINI - CTO, Milano, Italy;8. Laboratory of Experimental Pathology, Rizzoli Orthopedic Institute, Bologna, Italy |
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| Abstract: | The SWItch/Sucrose Non-Fermentable (SWI/SNF) complexes are ubiquitous ATP dependent chromatin remodeling complexes that provide epigenetic regulation of gene expressions across the genome. Different combination of SWI/SNF subunits allow tissue specific regulation of critical cellular processes. The identification of SMARCB1 inactivation in pediatric malignant rhabdoid tumors provided the first example that the SWI/SNF complex may act as a tumor suppressor. It is now estimated at least 20% of all human tumors contain mutations in the subunits of the SWI/SNF complex. This review summarizes the central nervous system tumors with alterations in the SWI/SNF complex genes. Atypical teratoid/rabdoid tumor (AT/RT) is a highly aggressive embryonal tumor genetically characterized by bi-allelic inactivation of SMARCB1, and immunohistochemically shows complete absence of nuclear expression of its protein product INI1. A small subset of AT/RT show retained INI1 expression but defects in another SWI/SNF complex gene SMARCA4. Embryonal tumors with medulloblastoma, pineoblastoma, or primitive neuroectodermal morphology but loss of INI1 expression are now classified as AT/RT. Cribriform neuroepithelial tumor (CRINET) is an intra or para-ventricular tumor that has similar SMARCB1 alterations as AT/RT but generally has a benign clinical course. Besides AT/RT and CRINET, compete loss of nuclear INI1 expression has also been reported in poorly differentiated chordoma and intracranial myxoid sarcoma within the central nervous system. Families with non-truncating SMARCB1 mutations are prone to develop schwannomatosis and a range of developmental syndromes. The schwannomas in these patients usually demonstrate a mosaic INI1 staining pattern suggestive of partial residual protein function. Finally, clear cell meningioma is a WHO grade II variant meningioma characterized by bi-allelic inactivation of the SMARCE1 gene and immunohistochemically show loss of its protein product BAF57 expression in tumor cell nuclei. |
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