Integrative analyses of rhabdoid tumors across all anatomical sites reveal subgroups with possible immune modulation through epigenetic dysregulation

Extra-cranial malignant rhabdoid tumors (MRTs) and cranial atypical teratoid RTs (ATRTs) are pediatric cancers driven by SMARCB1 loss. To understand biological relationships between MRTs and ATRTs, we performed integrative data analyses of 140 MRTs and 161 ATRTs, and detected features conserved between MRTs and the MYC subgroup of ATRTs, including global DNA hypomethylation and over-expression of HOX and mesenchymal development genes, thereby distinguishing them from other ATRT subgroups that exhibit neural-like features. Our analyses revealed five DNA-methylation subgroups associated with distinct anatomical sites, SMARCB1 alteration patterns, and distinct gene-expression and enhancer profiles. We also report on RT subgroups with expression patterns indicative of both increased immune infiltration and expression of immune checkpoint genes, which were confirmed using immunohistochemical techniques. Comparative analysis of the methyolme of eMRT and ATRT by methylation arrays