Identification and analyses of extra-cranial and cranial rhabdoid tumor molecular subgroups reveal tumors with cytotoxic T cell infiltration

Chun, H.-J. E. et al. (2019) Identification and analyses of extra-cranial and cranial rhabdoid tumor molecular subgroups reveal tumors with cytotoxic T cell infiltration. Cell Reports, 29(8), 2338-2354.e7. (doi: 10.1016/j.celrep.2019.10.013) (PMID:31708418) (PMCID:PMC6905433)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Lever, Dr Jake
• Authors: Chun, H.-J. E., Johann, P. D., Milne, K., Zapatka, M., Buellesbach, A., Ishaque, N., Iskar, M., Erkek, S., Wei, L., Tessier-Cloutier, B., Lever, J., Titmuss, E., Topham, J. T., Bowlby, R., Chuah, E., Mungall, K. L., Ma, Y., Mungall, A. J., Moore, R. A., Taylor, M. D., Gerhard, D. S., Jones, S. J.M., Korshunov, A., Gessler, M., Kerl, K., Hasselblatt, M., Frühwald, M. C., Perlman, E. J., Nelson, B. H., Pfister, S. M., Marra, M. A., and Kool, M.
• College/School: College of Science and Engineering > School of Computing Science
• Journal Name: Cell Reports
• Publisher: Elsevier (Cell Press)
• ISSN: 2211-1247
• ISSN (Online): 2211-1247
• Published Online: 07 November 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Cell Reports 29(8): 2338-2354.e7
• Publisher Policy: Reproduced under a Creative Commons License