Original ArticlesSellar Region Atypical Teratoid/Rhabdoid Tumors (ATRT) in Adults Display DNA Methylation Profiles of the ATRT-MYC SubgroupJohann, Pascal D. MD*,†,‡; Bens, Susanne MD§; Oyen, Florian∥; Wagener, Rabea PhD§; Giannini, Caterina MD¶; Perry, Arie MD#; Raisanen, Jack M. MD**; Reis, Gerald F. MD, PhD††; Nobusawa, Sumihito MD‡‡; Arita, Kazunori MD§§; Felsberg, Jörg MD∥∥; Reifenberger, Guido MD∥∥; Agaimy, Abbas MD¶¶; Buslei, Rolf MD##; Capper, David MD***; Pfister, Stefan M. MD*,†,‡; Schneppenheim, Reinhard MD, PhD∥; Siebert, Reiner MD§; Frühwald, Michael C. MD, PhD†††; Paulus, Werner MD‡‡‡; Kool, Marcel PhD*,†; Hasselblatt, Martin MD‡‡‡Author Information *Hopp-Children’s Cancer Center at the NCT Heidelberg †Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK) ‡Department of Pediatric Oncology and Hematology, University Hospital Heidelberg, Heidelberg §Institute of Human Genetics, University of Ulm and University Hospital of Ulm, Ulm ∥Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg ∥∥Institute of Neuropathology, Medical Faculty, Heinrich Heine University, and German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Düsseldorf ¶¶Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital Erlangen, Erlangen ##Department of Neuropathology, Sozialstiftung Bamberg, Bamberg ***Department of Neuropathology, Charité Universitätsmedizin Berlin, Berlin †††Swabian Children’s Cancer Center, Children’s Hospital Augsburg and EU-RHAB Registry, Augsburg ‡‡‡Institute of Neuropathology, University Hospital Münster, Münster, Germany ¶Department of Pathology, Mayo Clinic, Rochester, MN #Division of Neuropathology, UCSF Medical Center, San Francisco, CA **Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX ††Department of Pathology, Memorial Regional Hospital, Hollywood, FL ‡‡Department of Human Pathology, Gunma University Graduate School of Medicine, Gunma §§Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan Conflicts of Interest and Source of Funding: Supported by IZKF Münster (Ha3/019/15) and the DKFZ-Heidelberg Center for Personalized Oncology (DKFZ-HIPO). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Martin Hasselblatt, MD, Institute of Neuropathology, Pottkamp 2, Münster 48149, Germany (e-mail: firstname.lastname@example.org). The American Journal of Surgical Pathology: April 2018 - Volume 42 - Issue 4 - p 506-511 doi: 10.1097/PAS.0000000000001023 Buy SDC Metrics Abstract Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor predominantly encountered in infants. Mutations of the SMARCB1 gene are the characteristic genetic lesion. A small group of ATRT stands out clinically, because these tumors are located in the sellar region of adults. To investigate if sellar region ATRT in adults represents a molecular distinct entity, we characterized molecular alterations in 7 sellar region ATRTs in adults as compared with 150 pediatric ATRTs and 47 pituitary adenomas using SMARCB1 sequencing, multiplex ligation-dependent probe amplification and fluorescence in situ hybridization as well as DNA methylation profiling. The median age of the 6 female and 1 male patients was 56 years. On histopathologic examination, all tumors were malignant rhabdoid tumors showing loss of SMARCB1/INI1 protein expression. Two cases displayed compound heterozygous SMARCB1 point mutations, 3 cases showed heterozygous SMARCB1 deletions with point mutations of the other allele and 1 case a homozygous SMARCB1 deletion; in 1 case, underlying SMARCB1 alterations could not be identified. On unsupervised hierarchical cluster analysis of DNA methylation profiles, sellar region ATRTs did not form a distinct group, but clustered with ATRT-MYC, 1 of 3 recently described molecular subgroups of ATRT. On analysis of DNA methylation array intensity data, only 1 sellar region ATRT showed characteristic features of pediatric ATRT-MYC, that is, major copy number losses affecting the SMARCB1 region. In conclusion, these results suggest that sellar region ATRTs in adults form a clinically distinct entity with a different mutational spectrum, but epigenetic similarities with pediatric ATRTs of the ATRT-MYC subgroup. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.