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

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:

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

In order to access Controlled TARGET RT data using the links below, users must submit an application for Authorized Access via dbGaP as described on dbGaP’s TARGET Study Page. To begin the application process, please view the information and instructions provided on the dbGaP Authorized Access Login Page under “dbGaP Data Download”.

Supplemental Data Files

• GDC Manifests
  • Controlled-Access Data Download Manifest (5 Files)
  • Open-Access Data Download Manifest (10 Files)

• mRNA-Seq
  • TARGET RT mRNA-Seq Level 3 Data
  • TARGET RT mRNA-Seq Level 3 Data (Controlled)
  • TARGET RT mRNA-Seq Metadata
• miRNA-Seq
  • TARGET RT miRNA-Seq Level 3 Data
  • TARGET RT miRNA-Seq Metadata
• Bisulfite-Seq
  • TARGET RT Bisulfite-Seq Level 3 Data (Controlled)
  • TARGET RT Bisulfite-Seq Metadata
• ChIP-Seq
  • TARGET RT ChIP-Seq Level 3 Data (Controlled)
  • TARGET RT ChIP-Seq Metadata
• Methylation Array
  • TARGET RT Methylation Array Level 1 Data (Controlled)
  • TARGET RT Methylation Array Level 2 Data
  • TARGET RT Methylation Array Metadata
• WGS
  • TARGET RT WGS Level 3 Data (Controlled)
  • TARGET RT WGS Metadata
• Miscellaneous Files
  • TARGET RT Sample Matrices

Additional Resources

• OCG TARGET Data Matrix (link is external) Office of Cancer Genomics
• SRA - SRP012000 (link is external) NCBI

Instructions for Data Download

Open Access Data

1. Download the appropriate manifest file from the publication page
2. Use the manifest file to download data using the GDC Data Transfer Tool (DTT) or the GDC API
   • GDC DTT (Download, User's Guide)
   • GDC API (User’s Guide)

Controlled Access Data

1. Download the appropriate manifest file from the publication page
2. Download a token from the GDC Data Portal
   • GDC Data Portal (Launch, User’s Guide)
3. Use the manifest file and token to download data using the GDC DTT or the GDC API
   • GDC DTT (Download, User’s Guide)
   • GDC API (User’s Guide)

For assistance, please contact the GDC Help Desk: support@nci-gdc.datacommons.io