Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors

Cancer Cell. Volume 27, Issue 2: p.286-297, 9 February 2015 10.1016/j.ccell.2015.01.003

We report the most common single-nucleotide substitution/deletion mutations in favorable histology Wilms tumors (FHWTs) to occur within SIX1/2 (7% of 534 tumors) and microRNA processing genes (miRNAPGs) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs (discovery cohort) indicates that tumors with SIX1/2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations. Significantly decreased expression of mature Let-7a and the miR-200 family (responsible for mesenchymal-to-epithelial transition) in miRNAPG mutant tumors is associated with an undifferentiated blastemal histology. The combination of SIX and miRNAPG mutations in the same tumor is associated with evidence of RAS activation and a higher rate of relapse and death.

This study characterized TARGET cases as described below:

GE=gene expression; CN=copy number, TCS=targeted capture sequencing

In order to access Controlled TARGET WT 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

• GDC Manifests
  • Controlled-Access Data Download Manifest (8 Files)
  • Open-Access Data Download Manifest (25 Files)
  • WGS CGI Files Download Manifest (82 Files)

• Copy Number Array
  • TARGET WT Copy number array Level 1 Data (Controlled)
  • TARGET WT Copy number array Level 2 Data (Controlled)
  • TARGET WT Copy number array Level 3 Data
  • TARGET WT Copy number array Metadata
• Gene Expression Array
  • TARGET WT Gene expression array Level 1 Data
  • TARGET WT Gene expression array Level 2 Data
  • TARGET WT Gene expression array Level 3 Data
  • TARGET WT Gene expression array Level 4 Data
  • TARGET WT Gene expression array Metadata
• mRNA-Seq
  • TARGET WT mRNA-Seq Level 3 data
  • TARGET WT mRNA-Seq Level 3 data (Controlled)
  • TARGET WT mRNA-Seq Metadata
• miRNA-Seq
  • TARGET WT miRNA-Seq Level 3 Data
  • TARGET WT miRNA-Seq Metadata
• Whole Exome Sequencing
  • TARGET WT WXS Level 3 Data
  • TARGET WT WXS Level 3 Data (Controlled)
  • TARGET WT WXS Design
  • TARGET WT WXS Metadata
• Methylation Array
  • TARGET WT Methylation array Level 1 Data (Controlled)
  • TARGET WT Methylation array Level 2 Data
  • TARGET WT Methylation array Level 3 Data
  • TARGET WT Methylation array Level 4 Data
  • TARGET WT Methylation array Metadata
• Whole Genome Sequencing
  • TARGET WT WGS Level 3 Data
  • TARGET WT WGS Level 3 Data (Controlled)
  • TARGET WT WGS Level 4 Data
  • TARGET WT WGS Metadata
• Targeted Capture Sequencing
  • TARGET WT Targeted Capture Sequencing Level 3 Data (Controlled)
  • TARGET WT Targeted Capture Sequencing Design
  • TARGET WT Targeted Capture Sequencing Metadata
• Miscellaneous Files
  • TARGET WT Sample Matrices
  • TARGET WT CGI Requested Reports (Controlled)

Additional Resources

• TARGET-WT at SRA (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.