Nonsense mutation and inactivation of SMARCA4 (BRG1) in an atypical teratoid/rhabdoid tumor showing retained SMARCB1 (INI1) expression

Am J Surg Pathol. 2011 Jun;35(6):933-5. doi: 10.1097/PAS.0b013e3182196a39.


Atypical teratoid/rhabdoid tumors (AT/RTs) are highly aggressive brain tumors of early childhood poorly responding to therapy. The majority of cases show inactivation of SMARCB1 (INI1, hSNF5, BAF47), a core member of the adenosine triphosphate (ATP)-dependent SWI/SNF chromatin-remodeling complex. We here report the case of a supratentorial AT/RT in a 9-month-old boy, which showed retained SMARCB1 staining on immunohistochemistry and lacked genetic alterations of SMARCB1. Instead, the tumor showed loss of protein expression of another SWI/SNF chromatin-remodeling complex member, the ATPase subunit SMARCA4 (BRG1) due to a homozygous SMARCA4 mutation [c.2032C>T (p.Q678X)]. Our findings highlight the role of SMARCA4 in the pathogenesis of SMARCB1-positive AT/RT and the usefulness of antibodies directed against SMARCA4 in this diagnostic setting.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / therapy
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Codon, Nonsense*
  • Combined Modality Therapy
  • DNA Helicases / genetics*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Fatal Outcome
  • Gene Silencing
  • Humans
  • Infant
  • Male
  • Nuclear Proteins / genetics*
  • Rhabdoid Tumor / genetics
  • Rhabdoid Tumor / pathology*
  • Rhabdoid Tumor / therapy
  • SMARCB1 Protein
  • Teratoma / genetics
  • Teratoma / pathology*
  • Teratoma / therapy
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Chromosomal Proteins, Non-Histone
  • Codon, Nonsense
  • DNA-Binding Proteins
  • Nuclear Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases