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

Cell Rep. 2019 Nov 19;29(8):2338-2354.e7. doi: 10.1016/j.celrep.2019.10.013. Epub 2019 Nov 7.


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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • SMARCB1 Protein
  • SMARCB1 protein, human