SMARCB1

Overview

SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily B, Member 1), also known as SNF5 or INI1, encodes a core subunit of the SWI/SNF chromatin-remodeling complex. Biallelic inactivation of SMARCB1 is the defining molecular event of malignant rhabdoid tumors (MRT) and atypical teratoid/rhabdoid tumors (ATRT). Tumors with SMARCB1 loss are synthetic lethal with EZH2 activity and are targets for EZH2 inhibitor therapy.

Alterations observed in the corpus

  • Homozygous deletion of chr22q11.23 with biallelic loss of SMARCB1 expression identified in a hepatic rhabdoid tumor (MRTL) in the PIPseq pediatric precision sequencing program (n=101, Columbia University); designated as an EZH2-inhibitor target. PMID:28007021
  • Overexpression of ASCL1 with 22q11.21 LOH including SMARCB1 was diagnostic of ATRT and prognostic for improved outcome in the same cohort. PMID:28007021
  • SMARCB1 (INI1) protein expression retained by IHC in an EWSR1::BEND2 fusion sarcoma of the urinary bladder, ruling out rhabdoid/INI1-deficient differential diagnoses PMID:28199314.

Cancer types (linked)

  • MRTL: Biallelic SMARCB1 deletion (chr22q11.23) is the defining event in pediatric hepatic rhabdoid tumor; EZH2 inhibitor indicated. PMID:28007021
  • ATRT: 22q11.21 LOH including SMARCB1 alongside ASCL1 overexpression is diagnostic and associated with improved prognosis within ATRT. PMID:28007021

Co-occurrence and mutual exclusivity

  • Part of the SWI/SNF complex alongside SMARCA4 and SMARCC2; alterations in these genes collectively define rhabdoid phenotype tumors. PMID:28007021

Therapeutic relevance

  • EZH2 inhibitors are the designated targeted therapy for SMARCB1-deficient rhabdoid tumors (synthetic lethality); this was an actionable finding in the PIPseq pediatric cohort. PMID:28007021

Open questions

  • The prognostic distinction between SMARCB1-deleted hepatic rhabdoid tumor (MRTL) and ATRT in terms of EZH2-inhibitor response requires clinical trial evidence. PMID:28007021

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:28199314

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