Identification and Analyses of Extra-Cranial and Cranial Rhabdoid Tumor Molecular Subgroups Reveal Tumors with Cytotoxic T Cell Infiltration.

Abstract

Extra-cranial malignant rhabdoid tumors (MRTs) and cranial atypical teratoid RTs (ATRTs) are heterogeneous pediatric cancers driven primarily by SMARCB1 loss. To understand the genome-wide molecular relationships between MRTs and ATRTs, we analyze multi-omics data from 140 MRTs and 161 ATRTs. We detect similarities between the MYC subgroup of ATRTs (ATRT-MYC) and extra-cranial MRTs, including global DNA hypomethylation and overexpression of HOX genes and genes involved in mesenchymal development, distinguishing them from other ATRT subgroups that express neural-like features. We identify five DNA methylation subgroups associated with anatomical sites and SMARCB1 mutation patterns. Groups 1, 3, and 4 exhibit cytotoxic T cell infiltration and expression of immune checkpoint regulators, consistent with a potential role for immunotherapy in rhabdoid tumor patients.

• Authors: Hye-Jung E Chun, Pascal D Johann, Katy Milne, Marc Zapatka, Annette Buellesbach, Naveed Ishaque, Murat Iskar, Serap Erkek, Lisa Wei, Basile Tessier-Cloutier, Jake Lever, Emma Titmuss, James T Topham, Reanne Bowlby, Eric Chuah, Karen L Mungall, Yussanne Ma, Andrew J Mungall, Richard A Moore, Michael D Taylor, Daniela S Gerhard, Steven J M Jones, Andrey Korshunov, Manfred Gessler, Kornelius Kerl, Martin Hasselblatt, Michael C Frühwald, Elizabeth J Perlman, Brad H Nelson, Stefan M Pfister, Marco A Marra, Marcel Kool
• Journal: Cell reports (Cell Rep) Vol. 29 Issue 8 Pg. 2338-2354.e7 (11 19 2019) ISSN: 2211-1247 [Electronic] United States
• PMID: 31708418 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• SMARCB1 Protein
• SMARCB1 protein, human

Topics

• Child
• DNA Methylation (genetics, physiology)
• Female
• Humans
• Lymphocytes, Tumor-Infiltrating (metabolism, pathology)
• Male
• Mutation (genetics)
• Rhabdoid Tumor (metabolism, pathology)
• SMARCB1 Protein (genetics, metabolism)
• Skull Base Neoplasms (metabolism, pathology)
• T-Lymphocytes (metabolism, pathology)
• T-Lymphocytes, Cytotoxic (metabolism, pathology)
• Teratoma (metabolism, pathology)