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

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. TaylorDaniela 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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. Chun et al. report similarities between the MYC subgroup of cranial and extra-cranial rhabdoid tumors (RTs) at genetic, gene-expression, and epigenetic levels. They identify five DNA methylation subgroups of RTs across multiple organ sites, and some subgroups exhibit increased levels of immune cell infiltration and immune checkpoint expression.

Original languageEnglish (US)
Pages (from-to)2338-2354.e7
JournalCell reports
Issue number8
StatePublished - Nov 19 2019


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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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