TY - JOUR
T1 - Nonsense mutation and inactivation of SMARCA4 (BRG1) in an atypical teratoid/rhabdoid tumor showing retained SMARCB1 (INI1) expression
AU - Hasselblatt, Martin
AU - Gesk, Stefan
AU - Oyen, Florian
AU - Rossi, Sabrina
AU - Viscardi, Elisabetta
AU - Giangaspero, Felice
AU - Giannini, Caterina
AU - Judkins, Alexander R.
AU - Frühwald, Michael C.
AU - Obser, Tobias
AU - Schneppenheim, Reinhard
AU - Siebert, Reiner
AU - Paulus, Werner
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
KW - BRG1
KW - INI1
KW - SMARCA4
KW - SMARCB1
KW - atypical teratoid/rhabdoid tumor
UR - http://www.scopus.com/inward/record.url?scp=79957975801&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79957975801&partnerID=8YFLogxK
U2 - 10.1097/PAS.0b013e3182196a39
DO - 10.1097/PAS.0b013e3182196a39
M3 - Article
C2 - 21566516
AN - SCOPUS:79957975801
SN - 0147-5185
VL - 35
SP - 933
EP - 935
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 6
ER -