SMARCA2

Overview

SMARCA2 (BRM) is a catalytic subunit of the SWI/SNF chromatin remodeling complex. In the corpus, SMARCA2 mutations emerge specifically at relapse in fusion-negative rhabdomyosarcoma (FN-RMS), implicating chromatin remodeling disruption in treatment resistance.

Alterations observed in the corpus

  • SMARCA2 showed missense mutations and frameshift deletions in 24% of FN-RMS patients at relapse only (not at diagnosis); 4 different point mutations with no protein domain redundancy were identified, suggesting functional inactivation of SWI/SNF remodeling activity PMID:37730754.
  • Heterogeneous nuclear expression in both myoepithelial carcinomas (MEC1 and MEC2) by IHC PMID:36577525
  • Missense mutations in Helicase C domain (T1126I, G1132V, G1164W); frequency 5%; SWI/SNF catalytic subunit; identified as a CHASM driver in adenoid cystic carcinoma. PMID:23685749
  • 3 somatic missense mutations in adenoid cystic carcinoma discovery cohort (24 cases); part of the chromatin-remodeling gene cluster mutated in 12/24 cases in ACC; co-mutated with ARID1A, KDM6A, CREBBP, and other SWI/SNF members. PMID:23778141
  • SMARCA2 (BRM) is discussed as a synthetic-lethal vulnerability in SMARCA4-deficient SCCOHT; prior evidence (Oike et al. 2013) shows SMARCA2 silencing suppresses growth of SMARCA4-null cells PMID:24658004
  • Chromatin-remodelling gene (SWI/SNF complex) significantly mutated in HCC; SMARCA2 alteration enriched in alcohol-related HCC; part of the chromatin-remodeller pathway altered in 28% of cases. PMID:25822088
  • Part of SWI/SNF chromatin-remodelling lesions in >42% of pancreatic ductal adenocarcinoma cases (along with SMARCA4, SMARCC1, SMARCC2, ARID1A, ARID1B, PBRM1). PMID:25855536
  • SMARCA2 recurrently mutated in adenoid cystic carcinoma (ACC) of the salivary gland as a chromatin-regulator mutation alongside SMARCC1 and KDM6A PMID:26862087

Cancer types (linked)

  • RMS — relapse-specific mutations in FN-RMS (24%); absent at diagnosis, indicating acquired alteration under therapeutic pressure PMID:37730754.

Co-occurrence and mutual exclusivity

  • Relapse-acquired in the context of FN-RMS; concurrent relapse alterations included TP53 loss, BCOR, and RAS/PIK3CA pathway mutations PMID:37730754.

Therapeutic relevance

  • No direct targeted therapy reported in the corpus; SWI/SNF complex disruption at relapse warrants investigation of SMARCA2-directed or epigenetic strategies in relapsed FN-RMS PMID:37730754.

Open questions

  • Whether SMARCA2 mutations are detectable in ctDNA at relapse and whether they predict response or resistance to salvage therapies is not addressed in the corpus PMID:37730754.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:36577525

This page was processed by crosslinker on 2026-05-14. - PMID:23685749

This page was processed by crosslinker on 2026-05-14. - PMID:23778141

This page was processed by crosslinker on 2026-05-14. - PMID:24658004

This page was processed by crosslinker on 2026-05-14. - PMID:25822088

This page was processed by crosslinker on 2026-05-14. - PMID:25855536

This page was processed by crosslinker on 2026-05-14. - PMID:26862087

This page was processed by wiki-cli on 2026-05-14.