title: Nonsense mutation and inactivation of SMARCA4 (BRG1) in an atypical teratoid/rhabdoid tumor showing retained SMARCB1 (INI1) expression.
abstract: 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.
authors.affiliation: Institute of Neuropathology, University Hospital Münster, Domagkstrasse 19, Münster, Germany. hasselblatt@uni-muenster.de
authors.forename: Martin
authors.initials: M
authors.lastname: Hasselblatt
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Florian
authors.initials: F
authors.lastname: Oyen
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rossi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Viscardi
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.forename: Caterina
authors.initials: C
authors.lastname: Giannini
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Judkins
authors.forename: Michael C
authors.initials: MC
authors.lastname: Frühwald
authors.forename: Tobias
authors.initials: T
authors.lastname: Obser
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schneppenheim
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D018389:Codon, Nonsense; D003131:Combined Modality Therapy; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017809:Fatal Outcome; D020868:Gene Silencing; D006801:Humans; D007223:Infant; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D018335:Rhabdoid Tumor / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D000071796:SMARCB1 Protein; D013724:Teratoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases