Case ReportsNonsense Mutation and Inactivation of SMARCA4 (BRG1) in an Atypical Teratoid/Rhabdoid Tumor Showing Retained SMARCB1 (INI1) ExpressionHasselblatt, Martin MD*; Gesk, Stefan MD†,‡; Oyen, Florian§; Rossi, Sabrina MD∥; Viscardi, Elisabetta MD¶; Giangaspero, Felice MD♯,**; Giannini, Caterina MD, PhD††; Judkins, Alexander R. MD‡‡,§§; Frühwald, Michael C. MD, PhD∥∥; Obser, Tobias§; Schneppenheim, Reinhard MD, PhD§; Siebert, Reiner MD†,‡; Paulus, Werner MD*Author Information *Institute of Neuropathology, University Hospital Münster, Münster †Institute of Human Genetics, Christian-Albrechts-University Kiel ‡University Hospital Schleswig-Holstein, Campus Kiel §Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg ∥∥Pediatric Hospital, Klinikum Augsburg, Germany ∥Department of Pathology, Regional Hospital, Treviso ¶Department of Pediatrics, University of Padova ♯Department of Radiology, Oncology and Anatomic Pathology, University Sapienza, Rome, Italy **IRCCS Neuromed, Pozzilli (Is), Italy ††Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN ‡‡Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles §§Keck School of Medicine, University of Southern California, Los Angeles, CA M.H.'s and W.P.'s research on the molecular pathogenesis of AT/RT was supported by IZKF Münster (HA3/016/11). R.S. was supported by KinderKrebsInitiative (KKI) Buchholz/Holm-Seppensen. The study of RSch was supported by the “Fördergemeinschaft Kinderkrebszentrum Hamburg e.V.” Correspondence: Martin Hasselblatt, MD, Institute of Neuropathology, University Hospital Münster Domagkstr. 19, 48129 Münster, Germany (e-mail: email@example.com). The American Journal of Surgical Pathology: June 2011 - Volume 35 - Issue 6 - p 933-935 doi: 10.1097/PAS.0b013e3182196a39 Buy SDC Metrics 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. © 2011 Lippincott Williams & Wilkins, Inc.