Neuro-Oncology 22(5), 613–624, 2020 | doi:10.1093/neuonc/noz235 | Advance Access date 31 December 2019 613 © The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. Molecular subgrouping of atypical teratoid/rhabdoid tumors—a reinvestigation and current consensus Ben Ho, * Pascal D. Johann, * Yura Grabovska, * Mamy Jean De Dieu Andrianteranagna, Fupan Yao, Michael Frühwald, Martin Hasselblatt, Franck Bourdeaut, Daniel Williamson, # Annie Huang, # and Marcel Kool # Division of Hematology and Oncology, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada (B.H., A.H.); Hopp Children’s Cancer Center, Heidelberg, Germany (P.D.J., M.K.); Division of Pediatric Neuro-oncology, German Cancer Research Center and German Cancer Research Consortium, Heidelberg, Germany (P.D.J., M.K.); Department of Pediatric Hematology and Oncology, University Hospital Heidelberg, Heidelberg, Germany (P.D.J.); Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK (Y.G., D.W.); Departments of Genetics and of Oncopediatry and Young Adults, Curie Institute, Paris, France (M.J.D.D.A., F.B.); INSERM U830, Laboratory of Translational Research in Pediatric Oncology, SIREDO Pediatric Oncology Center, Curie Institute, Paris, France (M.J.D.D.A., F.B.); Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada (F.Y.); University Children’s Hospital Augsburg, Swabian Children’s Cancer Center, Augsburg, Germany (M.F.); Institute of Neuropathology, University Hospital Münster, Münster, Germany (M.H.) Corresponding Authors: Marcel Kool, PhD, Hopp Children’s Cancer Center (KiTZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany (m.kool@kitz-heidelberg.de); Annie Huang, MD PhD, The Hospital for Sick Children, Division of Hematology & Oncology, 555 University Ave, Toronto, Ontario, Canada M5G 1X8 (annie.huang@sickkids.ca). *Shared frst authors. #Shared senior authors. Abstract Background. Atypical teratoid/rhabdoid tumors (ATRTs) are known to exhibit molecular and clinical heteroge- neity even though SMARCB1 inactivation is the sole recurrent genetic event present in nearly all cases. Indeed, recent studies demonstrated 3 molecular subgroups of ATRTs that are genetically, epigenetically, and clinically distinct. As these studies included different numbers of tumors, various subgrouping techniques, and naming, an international working group sought to align previous fndings and to reach a consensus on nomenclature and clinicopathological signifcance of ATRT subgroups. Methods. We integrated various methods to perform a meta-analysis on published and unpublished DNA methyl- ation and gene expression datasets of ATRTs and associated clinicopathological data. Results. In concordance with previous studies, the analyses identifed 3 main molecular subgroups of ATRTs, for which a consensus was reached to name them ATRT-TYR, ATRT-SHH, and ATRT-MYC. The ATRT-SHH subgroup ex- hibited further heterogeneity, segregating further into 2 subtypes associated with a predominant supratentorial (ATRT-SHH-1) or infratentorial (ATRT-SHH-2) location. For each ATRT subgroup we provide an overview of its main molecular and clinical characteristics, including SMARCB1 alterations and pathway activation. Conclusions. The introduction of a common classifcation, characterization, and nomenclature of ATRT subgroups will facilitate future research and serve as a common ground for subgrouping patient samples and ATRT models, which will aid in refning subgroup-based therapies for ATRT patients. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Downloaded from https://academic.oup.com/neuro-oncology/article/22/5/613/5691191 by guest on 09 June 2021