SWI/SNF deficient central nervous system neoplasms.

Area of Science:

• Oncology
• Genetics
• Epigenetics

Background:

• SWItch/Sucrose Non-Fermentable (SWI/SNF) complexes are crucial ATP-dependent chromatin remodelers regulating gene expression.
• Alterations in SWI/SNF subunits are implicated in at least 20% of human cancers, highlighting their role as tumor suppressors.
• SMARCB1 inactivation in pediatric malignant rhabdoid tumors was the first evidence of SWI/SNF complexes' tumor suppressor function.

Purpose of the Study:

• To review central nervous system tumors associated with SWI/SNF complex gene alterations.
• To detail the genetic and immunohistochemical characteristics of these tumors.
• To explore the clinical spectrum of SWI/SNF-related central nervous system neoplasms.

Main Methods:

• Literature review of central nervous system tumors with SWI/SNF gene alterations.
• Analysis of genetic mutations (e.g., SMARCB1, SMARCA4, SMARCE1) and protein expression (e.g., INI1, BAF57).
• Classification of tumor types based on SWI/SNF alterations and morphology.

Main Results:

• Atypical teratoid/rhabdoid tumors (AT/RT) are characterized by SMARCB1 inactivation and loss of INI1 expression.
• Cribriform neuroepithelial tumors (CRINET) share SMARCB1 alterations with AT/RT but typically have a benign course.
• Loss of INI1 expression is also observed in poorly differentiated chordomas and intracranial myxoid sarcomas.
• SMARCE1 inactivation defines clear cell meningiomas, leading to loss of BAF57 expression.
• Families with SMARCB1 mutations can develop schwannomatosis and developmental syndromes.

Conclusions:

• SWI/SNF complex gene alterations are significant drivers in various central nervous system tumors.
• Specific SWI/SNF gene mutations correlate with distinct tumor types and clinical behaviors.
• Understanding these alterations is critical for diagnosis, classification, and therapeutic strategies in neuro-oncology.