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

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Cell Rep. Volume 29, Issue 8: p.:2338-2354, 19 November 2019, 10.1016/j.celrep.2019.10.013

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. Methylation was redone for 69 of the MRTs that were included Chun HJ et al. (2016) so that the platform would be consistent (Illumina Infinium Methylation EPIC 850K) for all cases in this study. 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.

This study characterized TARGET cases as described below:

40 Discovery Cases   29 Validation Cases
40 cases had mRNA-seq   25 cases had mRNA-seq
40 cases had miRNA-seq   26 cases had miRNA-seq
40 cases had WGBS   29 cases had WGBS
40 cases had methylation array   28 cases had methylation array
16 cases had ChIP-seq   19 cases had ChIP-seq
40 cases had WGS   29 cases had WGS

WGBS = Whole genome bisulfite sequencing, methylation array = Illumina’s Infinium MethylationEPIC (850K)

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