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

Date

2019

Authors

Chun, Hye-Jung E.
Johann, Pascal D.
Milne, Katy
Zapatka, Marc
Buellesbach, Annette
Ishaque, Naveed
Iskar, Murat
Erkek, Serap
Wei, Lisa
Tessier-Cloutier, Basile

Journal Title

Journal ISSN

Volume Title

Publisher

Cell Reports

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.

Description

Keywords

Malignant rhabdoid tumor, atypical teratoid rhabdoid tumor, pediatric cancer, SMARCB1, molecular subgroups, genomic and epigenomic dysregulation, HOX dysregulation, cytotoxic T cell infiltration, tumor-infiltrating immune cells

Citation

Chun, H.E., Johann, P.D., Milne, K., Zapatka, M., Buellesbach, A.,Ishaque, N., … Kool, M. (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. https://doi.org/10.1016/j.celrep.2019.10.013